Ethyl isocyanoacetate → Ethyl (20Z)-20-formamido-9alpha-hydroxy-3-oxopregna-4,17(20)-dien-21-oate

HRID 1613972Notes

Reaction equation

HRID 1613972 reaction equation
[N+:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[C-:2].CC(C)([O-:12])C.[K+].C[O:16][C:17]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@:31]2([OH:36])[CH2:30][CH2:29][C@@:27]2([CH3:28])[C@H:23]3[CH2:24][CH2:25][C:26]2=O)[CH:18]=1>O1CCCC1>[CH:2]([NH:1]/[C:3](=[C:26]1/[CH2:25][CH2:24][C@@H:23]2[C@:27]/1([CH3:28])[CH2:29][CH2:30][C@@:31]1([OH:36])[C@H:22]2[CH2:21][CH2:20][C:19]2[C@:32]1([CH3:35])[CH2:33][CH2:34][C:17](=[O:16])[CH:18]=2)/[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:12]

Participants

5

Reactant 3

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

Product 1

HCID 86746636Ethyl (20Z)-20-formamido-9alpha-hydroxy-3-oxopregna-4,17(20)-dien-21-oate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Ethyl isocyanoacetate (1.64 g) in dry tetrahydrofuran (8 ml) was added slowly to a stirred suspension of potassium tert. butoxide (1.71 g) in dry tetrahydrofuran (60 ml) so that the temperature did not rise above 5° C. A solution of 3-methoxy-9α-hydroxyandrosta-3,5-dien-17-one (3.22 g) in dry tetrahydrofuran (15 ml) was added dropwise at 0° C. and the mixture was stirred at room temperature for 4 hours. Most of tetrahydrofuran was removed under reduced pressure and the product was taken up in cold water, adjusted to pH 0.8 with 4N aqueous hydrochloric acid and extracted with chloroform. The combined chloroform extracts were dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the product dried under vacuum. Yield 3.55 g. NMR spectra showed predominantly the formation of the title compound together with small amounts of ethyl (20E)-20-formamido-9α-hydroxy-3-oxopregna-4,17(20)-dien-21-oate and tert. butyl (20Z)-20-formamide-9α-hydroxy- 3-oxopregna-4,17(20)-dien-21-oate. The compounds were isolated through chromatography and separately identified through spectral data.

Workup

  1. customdid not rise above 5° C
  2. customMost of tetrahydrofuran was removed under reduced pressure
  3. extractionextracted with chloroform
  4. dry with materialThe combined chloroform extracts were dried over anhydrous magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe product dried under vacuum
  7. customThe compounds were isolated through chromatography

Sources & evidence

ORD record
ord-19abff8d4deb4e7caf0602d1ed62d0df
Source dataset
uspto-grants-1993_03
Patent number
US05194602

Reaction notes

Loading…