(R)-2-Methyl-CBS-oxazaborolidine → (S)-2-(4-t-butyldimethylsilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl)-1-cyclopentenyl-1-hydroxyethane

HRID 260124

Reaction equation

HRID 260124 reaction equation
[CH:1]1([C:6]([CH2:8][C:9]2[C:10]([O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])=[C:11]3[C:15](=[C:16]([CH3:20])[C:17]=2[CH2:18][CH3:19])[CH2:14][O:13][C:12]3=[O:21])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1>C1(C)C=CC=CC=1>[Si:23]([O:22][C:10]1[C:9]([CH2:8][C@@H:6]([C:1]2[CH2:5][CH2:4][CH2:3][CH:2]=2)[OH:7])=[C:17]([CH2:18][CH3:19])[C:16]([CH3:20])=[C:15]2[C:11]=1[C:12](=[O:21])[O:13][CH2:14]2)([C:26]([CH3:27])([CH3:28])[CH3:29])([CH3:25])[CH3:24]

Participants

4

Reactant 2

HCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 53886302Cyclopentyl (4-t-butyldimethylsilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl methyl)methanone

Product 1

HCID 70213482(S)-2-(4-t-butyldimethylsilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl)-1-cyclopentenyl-1-hydroxyethane

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-30 °C

Procedure

Cyclopentyl (4-t-butyldimethylsilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl methyl)methanone (4.2 g) was treated with a 1M toluene solution of (R)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo-[1,2-c][1,3,2]oxazaborole (3 ml). The toluene was evaporated in vacuo and methylene chloride added (2 ml). The reaction mixture was cooled to -30° C. and borane/dimethyl sulfide (0.33 ml) was added three times at 45 minute intervals. The reaction mixture was stirred 16 hours at -30° C. and quenched by addition of 1M hydrogen chloride/ether (3 ml). Toluene was added (10 ml) and the solution filtered, diluted with ether (200 ml), washed with aqueous hydrochloric acid, aqueous sodium bicarbonate and brine. Drying and evaporation gave an oil which was purified by silica gel chromatography to give (S)-2-(4-t-butyldimethylsilyloxy-1,3-dihydro-6-ethyl-7-methyl-3-oxoisobenzofuran-5-yl)-1-cyclopentenyl-1-hydroxyethane. Further purification by crystallization from t-butylmethyl ether gave material with an enantiomeric excess of 97.8% (Chiracel OD-H, 85:15 hexane:i-propanol, 0.8 ml/minute, minor 8.3 minutes, major 9.2 minutes).

Workup

  1. customThe toluene was evaporated in vacuo and methylene chloride
  2. additionadded (2 ml)
  3. additionborane/dimethyl sulfide (0.33 ml) was added three times at 45 minute intervals
  4. customquenched by addition of 1M hydrogen chloride/ether (3 ml)
  5. additionToluene was added (10 ml)
  6. filtrationthe solution filtered
  7. additiondiluted with ether (200 ml)
  8. washwashed with aqueous hydrochloric acid, aqueous sodium bicarbonate and brine
  9. customDrying
  10. customevaporation
  11. customgave an oil which
  12. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-3e0a60fab889430b9a0f026dcb081e32
Source dataset
uspto-grants-1996_06
Patent number
US05525602

Linked notes

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