Isobutyric Acid → 3alpha-Isobutyloxy-5alpha-pregnan-20-one

HRID 232807Notes

Reaction equation

HRID 232807 reaction equation
[OH:1][C@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[CH2:17][CH2:16][C@@:15]2([CH3:23])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:43](O)(=O)[CH:44]([CH3:46])[CH3:45]>O1CCCC1>[CH2:43]([O:1][C@@H:2]1[CH2:21][CH2:20][C@@:19]2([CH3:22])[C@@H:4]([CH2:5][CH2:6][C@@H:7]3[C@@H:18]2[CH2:17][CH2:16][C@@:15]2([CH3:23])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C:12](=[O:14])[CH3:13])[CH2:3]1)[CH:44]([CH3:46])[CH3:45]

Participants

5

Reactant 3

HCID 6590Isobutyric Acid2×HCID 11776Triphenylphosphine2×HCID 92787Isopregnanolone

Product 1

HCID 677076653alpha-Isobutyloxy-5alpha-pregnan-20-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 3β-hydroxy-5α-pregnan-20-one (8 g, 318.5 g/m, 25 mmol) in 200 mL of freshly distilled tetrahydrofuran (THF), triphenylphosphine (9.88 g, 262.3 g/m, 38 mmol), and isobutyric acid (3.5 mL) were added. To this stirred reaction mixture at room temperature was added a solution of diisopropylazidodicarboxylate (DIAD, 7.42 mL, 1.027 g/mL, 202.2 g/m, 38 mmol) in 75 mL of THF dropwise over a period of 10 minutes. The solution was stirred overnight. TLC indicated that the reaction was not complete. Triphenylphosphine (6.58 g), DIAD (4.94 mL), and isobutyric acid (2.33 mL) were added to the reaction and allowed to stir at room temperature for an additional 3 hours. TLC indicated complete reaction. The excess THF was evaporated and the residue was purified by column chromatography on silica gel with 90:10 hexane:ethyl acetate elution to give 7.3 g (346.5 g/m, 83.9%).

Workup

  1. customTo this stirred reaction mixture at room temperature
  2. stirringto stir at room temperature for an additional 3 hours
  3. customreaction
  4. customThe excess THF was evaporated
  5. customthe residue was purified by column chromatography on silica gel with 90:10 hexane
  6. washethyl acetate elution
  7. customto give 7.3 g (346.5 g/m, 83.9%)

Sources & evidence

ORD record
ord-1f5dd7875b6d478b92a2668e133eb04e
Source dataset
uspto-grants-1997_01
Patent number
US05591733

Reaction notes

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