Water → (3beta,5alpha)-21-Bromo-3-hydroxypregnane-11,20-dione

HRID 233502Notes

Reaction equation

HRID 233502 reaction equation
C(Cl)(=O)C.[OH:5][C@H:6]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@@H:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:22]2[C:21](=[O:27])[CH2:20][C@@:19]2([CH3:28])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C:16](=[O:18])[CH3:17])[CH2:7]1.[Br:29]Br.O>CO>[Br:29][CH2:17][C:16](=[O:18])[C@@H:15]1[C@:19]2([CH3:28])[C@H:12]([C@H:11]3[C@H:22]([C:21](=[O:27])[CH2:20]2)[C@:23]2([CH3:26])[C@H:8]([CH2:7][C@@H:6]([OH:5])[CH2:25][CH2:24]2)[CH2:9][CH2:10]3)[CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 24408BromineHCID 101789(3β,5α)-3-Hydroxypregnane-11,20-dione

Product 1

HCID 10621559(3beta,5alpha)-21-Bromo-3-hydroxypregnane-11,20-dione

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Acetyl chloride (9.71 ml) was added to a stirred solution of (3β,5α)-3-hydroxypregnane-11,20-dione (97.1 g) [prepared as described by Cameron et al., J. Chem. Soc., 1955, 2807] in methanol (2.4 l) and a solution of bromine (18.5 ml) in methanol (1 l) was then added over 30 min at room temperature. The reaction mixture was poured into water (30 l) and the precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After drying the solution over sodium sulfate, the solvent was removed under reduced pressure to give crude (3β,5α)-21-bromo-3-hydroxypregnane-11,20-dione (120 g). δ (CDCl3) 0.61 (s,3H), 1.02 (s,3H), 3.00-3.20 (m,1H), 3.49-3.62 (m,2H) and 3.85 (s,2H). Potassium acetate (240 g), potassium iodide (6 g) and glacial acetic acid (250 ml) were added to a solution of (3β,5α)-21-bromo-3-hydroxypregnane-11,20-dione (120 g) in acetone (4.8 l) and the mixture was heated under reflux for 3 h. The reaction mixture was poured into water (50 l) and the precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After drying the solution over sodium sulfate, the solvent was removed under reduced pressure. The residue was chromatographed over silica gel and the purified product was crystallised from diethyl ether to give (3β,5α)-21-(acetyloxy)-3-hydroxypregnane-11,20-dione (26 g) m.p. 163°-165° C.; [α]D +103.3° (c 0.97). 4-Toluenesulfonyl chloride (52 g) was added to a solution of (3β,5α)-21-(acetyloxy)-3-hydroxypregnane-11,20-dione (26 g) in pyridine (260 ml) and the solution was stirred for 4 h at room temperature. The reaction mixture was poured into water (2.6 l) and the precipitated solid was filtered off, washed with water and dissolved in dichloromethane. After drying the solution over sodium sulfate, the solvent was removed under reduced pressure. Crystallisation of the residue from methanol gave (3β,5α)-21-(acetyloxy)-3-{[(4-methylphenyl)sulfonyl]oxy}pregnane-11,20-dione (35 g). m.p. 155°-156° C.; [α]D +62.4° (c 1.11).

Workup

  1. filtrationthe precipitated solid was filtered off
  2. washwashed with water
  3. dissolutiondissolved in dichloromethane
  4. dry with materialAfter drying the solution over sodium sulfate
  5. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f93154ac388c4923ac3c07d435e456a9
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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