Ammonium Chloride → Ethyl (20Z)-20-formamido-9alpha-hydroxy-3-methoxypregna-3,5,17(20)-trien-21-oate

HRID 1613973Notes

Reaction equation

HRID 1613973 reaction equation
CC(C)([O-:4])C.[K+].[N+:7]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])#[C-:8].[OH:15][C@:16]12[CH2:33][CH2:32][C@@:30]3([CH3:31])[C@@H:26]([CH2:27][CH2:28][C:29]3=O)[C@@H:25]1[CH2:24][CH:23]=[C:22]1[C@:17]2([CH3:37])[CH2:18][CH2:19][C:20]([O:35][CH3:36])=[CH:21]1.[Cl-].[NH4+]>O1CCCC1>[CH:8]([NH:7]/[C:9](=[C:29]1/[CH2:28][CH2:27][C@@H:26]2[C@:30]/1([CH3:31])[CH2:32][CH2:33][C@@:16]1([OH:15])[C@H:25]2[CH2:24][CH:23]=[C:22]2[C@:17]1([CH3:37])[CH2:18][CH2:19][C:20]([O:35][CH3:36])=[CH:21]2)/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:4]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 533707Ethyl isocyanoacetateHCID 108600603-Methoxy-9alpha-hydroxyandrosta-3,5-dien-17-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 86746637Ethyl (20Z)-20-formamido-9alpha-hydroxy-3-methoxypregna-3,5,17(20)-trien-21-oateYield 22.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Potassium tert. butoxide (1.71 g) was added to dry tetrahydrofuran (60 ml) under nitrogen. The solution was cooled to 0° C. and a solution of ethyl isocyanoacetate (1.64 g) in tetrahydrofuran (10 ml) was added dropwise, while keeping the temperature below 0° C. Next, a solution of 9α-hydroxy-3-methoxyandrosta-3,5-dien-17-one (3.21 g) in tetrahydrofuran (60 ml) was added. After stirring for 5 hours at room temperature the mixture was poured into 400 ml of saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layers were washed three times with water, dried (MgSO4) and concentrated under reduced pressure. The crude product (3.20 g) was purified by chromatography (silica gel, toluene/acetone 4/1 containing 0.1% triethylamine) to provide 0.99 g of the title compound. NMR spectra showed the formation of the Z-isomer of the title compound as a mixture of the two rotamer forms of the 20-formamido group.

Workup

  1. customthe temperature below 0° C
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed three times with water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product (3.20 g) was purified by chromatography (silica gel, toluene/acetone 4/1 containing 0.1% triethylamine)

Sources & evidence

ORD record
ord-ec1702c06b8e4e89ac07e790e4ccbb2d
Source dataset
uspto-grants-1993_03
Patent number
US05194602

Reaction notes

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