Valine methyl ester, -, hydrochloride

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

To a 5 L 3-neck round bottom flask was added the crude carbonylbenzyloxy-3-aminopropanal (115 g, 0.555 mol) followed by addition of water (400 mL) and methanol (1600 mL). The reaction mixture was maintained at 25°C throughout the course of the reaction. After the solution became homogeneous. (S)-Valine methyl ester hydrochloride (90.2 g, 0.538 mol) was added in one portion followed by rapid addition of sodium acetate trihydrate (151 g, 1.11 mol) and sodium cycanoborohydride (73.2 g, 1.17 mol). The reaction mixture was allowed to stir at room temperature for 0.5 hour and was concentrated in vacuo. To this solution, saturated aq sodium bicarbonate (400 mL) was added and the mixture was extracted with isopropyl acetate (1 L). The organic layer was washed with water, dried over sodium sulfate, and concentrated to yield 150 g of crude product, which was dissolved in isopropyl acetate (300 mL) and heptane (2400 mL). Dry HCI was bubbled in and an oily solid precipitated out of solution. The liquid was decanted away from and the solid was dissolved in dichloromethane (3 L). The solution was washed with water (600 mL) and saturated aq sodium bicarbonate (600 mL) and dried over sodium sulfate. It was concentrated in vacuo to yield 105 g (59%) of N-(N-(benzyloxycarbonyl-3-amino)-propyl)valine methyl ester as a light yellow oil. 

L)-Valine methyl ester hydrochloride 2 -Cyanobiphenyl-4-carbaldehyde Sodium cyanoborohydride... 

L-Valine methyl ester hydrochloride Valine, methyl ester, hydrochloride, L-(8) L-Valine, methyl ester, hydrochloride (9) (6306-52-1)... 

In 1981, Hirao and others reported that the chiral borane-amine complex 25a, derived from (S)-prolinol and 1 equivalent of BH3 THF, enantioselec-tively reduced propiophenone to afford (R )-l -phenyl-1 -propanol (26) in 44% ee9 (Scheme 4.3h). The chiral complex 25b was even better than 25a, affording the same secondary alcohol in 60% ee. Two years after the initial disclosure, Hirao et al. uncovered a new catalyst system that improved the previous experimental conditions dramatically10 (Scheme 4.3i). When the chiral aminoalcohol 27, prepared from (S)-valine methyl ester hydrochloride and phenylmagnesium bromide, was used along with 2 equivalents of BH3 THF, the enantioselectivity of the alcohol 26 jumped to 94% ee. In addition, the reaction time was shortened to 2 hours. 

The Step 4 product (14.4 mmol) was dissolved in 160 ml THF and treated with 5 A molecular sieves (16 g) and L-valine methyl ester hydrochloride (28.8 mmol), then stirred 30 minutes at ambient temperature. The solution was further treated with the dropwise addition of sodium cyanoborohydride (14.4 mmol) in 18 ml methyl alcohol at 0—5°C and the mixture stirred overnight at ambient temperature. The solution was concentrated, the residue purified by chromatography using EtOAc/n-heptane, 1 2, and 4.41 g of product isolated as an amorphous solid... 

Preparative Methods from valine methyl ester hydrochloride and excess Phenylmagnesium Bromide in 56% yield. ... 

Thus, in a model reaction, valine methyl ester hydrochloride 732 was reacted with triphosgene in the presence of diisopropylethylamine (DIEA) in dichloromethane at room temperature for 30 min to give the intermediate 733. Serine benzyl ester hydrochloride 734 and DIEA in dichloromethane were then added over a period of 10 min. Product 735 was obtained in 89% yield as a result of a typical sequential, three-component reaction. The reaction can be successfully applied to various other amines bearing multiple functionalities, and exhibits high selectivity for N-nudeophiles amines (primary and/or secondary) bearing an unprotected primary or secondary hydroxy group can be used directly (85-88% yield). 

Typical procedure. Unsymmetrical urea 1012 [507] Triphosgene (110 mg, 0.37 mmol) was dissolved in dichloromethane (2 mL). A mixture of valine methyl ester hydrochloride 1009 (167.5 mg, 1 mmol) and diisopropylethylamine (DIEA, 378 pL, 2.2 mmol) in dichloromethane (3.5 mL) was slowly added to the stirred solution of triphosgene over a period of 30 min using a syringe pump. After a further 5 min of... 

Scheme 17.22 Cul and AglOa catalysed oxidative amidation of benzaldehyde with (i )-valine methyl ester hydrochloride.

Valine methyl ester, (S)-, hydrochloride Benzyl chloroformate Palladium hydroxide... 

The iminium salt 132, generated from benzylamine hydrochloride and aqueous formaldehyde, reacts with cyclopentadiene during 3 h at room temperature to give, after basification, the cycloadduct 133 in nearly quantitative yield (equation 70). Other examples of this reaction are shown in equations 71-75. The separable diastereomers 134 and 135 are formed in the ratio 4 1 from cyclopentadiene, (—)-a-methylbenzylamine hydrochloride and aqueous formaldehyde in a combined yield of 86% (equation 75)62. Hydrochlorides 136 of methyl esters of natural amino acids [(S )-valine, (S )-isoleucine] react with cyclopentadiene and formaldehyde in aqueous THF to produce mixtures of the diastereomers 137 and 138, in which the former predominate (equation 76)63. 

The present procedure for the preparation of oxazolidinone 3 is a variation of the procedures described by Luche" and Davies. Yields have been substantially enhanced by improving the purification procedures. The preparation of 3 starting from valine methyl or ethyl ester hydrochloride has been described by several authors. > > > These procedures suffer from moderate yields for the Grignard addition step and some of them use hazardous reagents like phosgene. 

---