Norethindrone acetate

98 grams of 17-ethinyl-19-nor-testosterone (norethindrone) are suspended in 30 cc of acetic anhydride and a solution of 1.9 grams of p-toluenesulfonic acid in 19 cc of acetic anhydride is gradually added while cooling and stirring. Complete dissolution takes place after about one hour. After additional 30 to 60 minutes, a thick, pasty mass separates. The reaction is permitted to continue for a total period of 5 hours, whereupon water is added to the reaction mixture and the 3-enol-17-diacetate which separates after stirring for 

Chemical Abstracts Registry No. 51-98-9 Trade Name Manufacturer 

Noreth indrone Acetic anhydride Hydrogen chloride 

1 to 2 hours is filtered off, mashed until neutral and dried in vacuo over calcium chloride at room temperature. 

In order to prepare the monoacetate, the crude diacetate is suspended in 150 cc of methanol and, after adding 1.5 cc, concentrated hydrochloric acid, heated to boiling for 15 minutes in a nitrogen atmosphere. The crude monoacetate mhich separates upon the addition of meter after cooling is filtered off, meshed end dried in vacuo over calcium chloride at room temperature. The pure 17-ecetete, obtained after repeated recrystellizetions from methylene chloride/hexane has a MP of 161° to 162°C. 

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Norethindrone may be recrystakhed from ethyl acetate (111). It is soluble in acetone, chloroform, dioxane, ethanol, and pyridine slightly soluble in ether, and insoluble in water (112,113). Its crystal stmcture has been reported (114), and extensive analytical and spectral data have been compiled (115). Norethindrone acetate can be recrystakhed from methylene chloride/hexane (111). It is soluble in acetone, chloroform, dioxane, ethanol, and ether, and insoluble in water (112). Data for identification have been reported (113). The preparation of norethindrone (28) has been described (see Fig. 5). Norethindrone acetate (80) is prepared by the acylation of norethindrone. Norethindrone esters have been described ie, norethindrone, an appropriate acid, and trifiuoroacetic anhydride have been shown to provide a wide variety of norethindrone esters including the acetate (80) and enanthate (81) (116). 

In further modifications of these norprogestins, reaction of norethindrone with acetic anhydride in the presence of p-toluene-sulfonic acid, followed by hydrolysis of the first-formed enol acetate, affords norethindrone acetate (41). This in turn affords, on reaction with excess cyclopentanol in the presence of phosphorus pentoxide, the 3-cyclopentyl enol ether (42) the progestational component of Riglovic . Reduction of norethindrone affords the 3,17-diol. The 33-hydroxy compound is the desired product since reactions at 3 do not show nearly the stereoselectivity of those at 17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium aluminum-tri-t-butoxide. Acetylation of the 33,173-diol iffords ethynodiol diacetate, one of the most potent oral proves tins (44). ... 

Melengestrol Acetate Norethindrone Norethindrone Acetate Norethinodrel... 

Millevit - Cyanocobalamin Milliderm - Hydrocortisone Milligynon - Norethindrone acetate Milontin - Phensuximide Miltaun - Meprobamate Miltown - Meprobamate Mllurit - Allopurinol... 

Activella—estradiol, norethindrone acetate CombiFhtch—estradiol, norethindrone Femhrt—ethinyl estradiol, norethindrone acetate Ortho-Pretest—estradiol, norgestimate Premephase—conjugated estrogens, medroxyprogesterone acetate... 

Ortho Tri-Cyclen (norgestimate/ethinyl estradiol) and Estrostep Fe (norethindrone acetate/ethinyl estradiol) both have an approved indication for treatment of moderate acne vulgaris in females 15 years of age or older desiring contraception who have failed topical antiacne medication. 

Oral contraceptives containing both an estrogen and progestin are used as an alternate treatment for moderate acne in women. Contraceptive agents currently FDA approved for this indication include norgestimate with ethinyl estradiol and norethindrone acetate with ethinyl estradiol. 

Dydrogesterone0 Medroxyprogesterone acetate Micronized progesterone Norethisterone0 Norethindrone acetate NorgestreP LevonorgestreF... 

CEE, conjugated equine estrogens MPA, medroxyprogesterone acetate NETA, norethindrone acetate. 

Speroff L, Symons J, Kempfert N et al. (2000) Femhrt study investigators. The effect of varying low-dose combinations of norethindrone acetate and ethinyl estradiol (femhrt) on the frequency and intensity of vasomotor symptoms. Menopause7 383-390... 

NORETHINDRONE ACETATE Norethindrone acetate differs from norethindrone only in potency the acetate is approximately twice as potent. 

Pregnancy Category D (progesterone injection) Catego/y X(norethindrone acetate). Use is not recommended. See Warning Box. 

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