Water → HCID 10506735, compound

HRID 233504Notes

Reaction equation

HRID 233504 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:12]([O:15][CH2:16][C:17](=[O:39])[C@@H:18]1[C@:35]2([CH3:36])[C@H:21]([C@H:22]3[C@H:32]([C:33](=[O:37])[CH2:34]2)[C@:30]2([CH3:31])[C@H:25]([CH2:26][C@@H:27]([OH:38])[CH2:28][CH2:29]2)[CH2:24][CH2:23]3)[CH2:20][CH2:19]1)(=[O:14])[CH3:13].O>N1C=CC=CC=1>[C:12]([O:15][CH2:16][C:17](=[O:39])[C@@H:18]1[C@:35]2([CH3:36])[C@H:21]([C@H:22]3[C@H:32]([C:33](=[O:37])[CH2:34]2)[C@:30]2([CH3:31])[C@H:25]([CH2:26][C@@H:27]([O:38][S:7]([C:4]4[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=4)(=[O:9])=[O:8])[CH2:28][CH2:29]2)[CH2:24][CH2:23]3)[CH2:20][CH2:19]1)(=[O:14])[CH3:13]

Participants

5

Reactant 3

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 10762994HCID 10762994, compound

Product 1

HCID 10506735HCID 10506735, compoundYield 96.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

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
  6. customCrystallisation of the residue from methanol

Sources & evidence

ORD record
ord-e32a24dd0db54e248f443c2ca14547a0
Source dataset
uspto-grants-1997_01
Patent number
US05593983

Reaction notes

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