Ammonia → Estradiol 3-methyl ether

HRID 1077213

Reaction equation

HRID 1077213 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C:17]3[CH2:16][CH2:15][C@@:13]4([CH3:14])[C@@H:9]([CH2:10][CH2:11][C@@H:12]4[OH:21])[C:8]=3[CH2:7][CH2:6][C:5]=2[CH:4]=1.N.NC1C=CC=CC=1.[Li].[Cl-].[NH4+]>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C@@H:12]([OH:21])[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 6115AnilineHCID 25517Ammonium ChlorideHCID 3028194LithiumHCID 110552063-Methoxyestra-1,3,5(10),8-tetraen-17beta-ol

Product 1

HCID 246206Estradiol 3-methyl etherYield 31.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add dl-3-methoxyestra-1,3,5(10),8-tetraen-17β-ol (37.5 g) in tetrahydrofuran (350 ml) to a stirred solution of liquid ammonia (1 liter) and aniline (45 ml). Add lithium (2 g), stir for 30 minutes, and then add ammonium chloride (20 g) followed by water. Extract with ether-benzene (1:1) and wash the organic solution with water, excess 3N hydrochloric acid, water and dry. Evaporate the solvent and recrystallize the residue from ethyl acetate-hexane to obtain dl-3-methoxyestra-1,3,5(10)-trien-17β-ol (12 g), m.p. 121-124°; ultraviolet absorption peak at 278 mμ (ε1,810); infrared maxima at 3.0 μ, 6.2 μ, 6.75 μ.

Workup

  1. extractionExtract with ether-benzene (1:1)
  2. washwash the organic solution with water, excess 3N hydrochloric acid, water
  3. customdry
  4. customEvaporate the solvent
  5. customrecrystallize the residue from ethyl acetate-hexane

Sources & evidence

ORD record
ord-d4b607b6e1e14a5dbe63e47e523ca206
Source dataset
uspto-grants-1976_05
Patent number
US03959322

Linked notes

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