Semi-synthetic Aspects of the Morphine Alkaloids

Reagents (i) Hg(OAc)2,MeOH,(ii)AcOH or NaBH4 3M HCOjH, (iii)3M HCOjH and HCI, CHjClj, HO, (iv) NaBH4, MeOH 

Codeine has been demethylated either by reaction with boron tribromide in chioroform at ambient temperature in 91% yield (ref. 164) or by treatment with sodium propylmercaptide in DMF at 125 C in 80% yield (ref. 165) to give morphine, both procedures representing considerable improvements on the former method with pyridine hydrochloride (ref. 166). 

Reagents (i) 2Br2,AcOH CHCI3, HO, (ii)AcOH, NaOAc.Pd-C.Hj, Oii) H(OEt 3, MeOH, H ,(iv) 4-TSA.CHCI3, (v)HBr-H20, (vi) KOBu, DMSO, (vii) 3M AcOH, (viii) NaBH. MeOH 

For the preparation of codeine from morphine a number of methylation procedures are available among which the use of trimethylammonium salts is customary and has been referred to in Chap. 4. 

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