Water → (20S)-4-amino-21-hydroxy-20-methylpregna-4,6-dien-3-one benzoate

HRID 2082415Notes

Reaction equation

HRID 2082415 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1[C:12]23[C@:28]([CH3:33])([CH2:29][CH2:30][C:31](=[O:32])[CH:11]12)[C@@H:27]1[C@H:15]([C@H:16]2[C@:24]([CH3:34])([CH2:25][CH2:26]1)[C@@H:19]([C@H:20]([CH3:23])[CH2:21][OH:22])[CH2:18][CH2:17]2)[CH2:14][CH2:13]3.[N-:35]=[N+]=[N-].[Na+].S(=O)(=O)(O)O.O>CS(C)=O>[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:35][C:11]1[C:31](=[O:32])[CH2:30][CH2:29][C@@:28]2([CH3:33])[C:12]=1[CH:13]=[CH:14][C@@H:15]1[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:34])[C@H:16]1[CH2:17][CH2:18][C@@H:19]2[C@H:20]([CH3:23])[CH2:21][OH:22]

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 33557Sodium AzideHCID 86745921(20S)-4,5-epoxy-21-hydroxy-20-methylpregnan-3-one benzoate

Product 1

HCID 67744905(20S)-4-amino-21-hydroxy-20-methylpregna-4,6-dien-3-one benzoateYield 80.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a vigorously stirred solution of (20S)-4,5-epoxy-21-hydroxy-20-methylpregnan-3-one benzoate (1.0 g, 2.22 mmole) in dimethyl sulfoxide (35 mL), heated to 60° C, there was added sodium azide (2.7 g) and the concentrated sulfuric acid (0.2 mL). The mixture was quickly brought to a temperature of 100° C. and held at that temperature for 1 hour. The cooled mixture was then poured onto cold water (250 mL). The resulting mixture was extracted with ether (300 mL) and the ether solution was washed with brine, dried over magnesium sulfate and filtrate and the filtrate was concentrated to give a yellow solid which was purified by chromatography to give (20S)-4-amino-21-hydroxy-20-methylpregna-4,6-dien-3-one benzoate (0.8 g, 80.1%) melting at 163°-167° C. with decomposition. IR 3470, 3366, 1718, 1682 (m), 1656, 1608 (m), 1586 (m), 1567 (m), 1274, 1268, 718 cm-1 ; MS (CI) 448 (100%, M+1), 326 (35%, M+1-PhCOOH); 1H NMR (CDCl3) δ0.82 (3H, s, C18 -Me), 1.07 (s, C19 -Me), 1.15 (d, C22 -Me), 3.71 (2H, v br, NH2), 4.07 (1H, dd, 1/2C21 -CH2), 4.35 (1H, dd, 1/2C21 -CH2), 5.98 (1H dd), 6.30 (1H dd), 7.35 (2H, t), 7.57 (1H, t), 8.04 (2H, dd).

Workup

  1. customwas quickly brought to a temperature of 100° C.
  2. extractionThe resulting mixture was extracted with ether (300 mL)
  3. washthe ether solution was washed with brine
  4. dry with materialdried over magnesium sulfate and filtrate
  5. concentrationthe filtrate was concentrated
  6. customto give a yellow solid which
  7. customwas purified by chromatography

Sources & evidence

ORD record
ord-3464253b931d4fd48e6980b0b8d39c39
Source dataset
uspto-grants-1993_02
Patent number
US05189032

Reaction notes

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