Tetrahydrofuran → [(3R,5R)-3,5-Bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy4-methylenecyclohexyl]methanol

HRID 2121322Notes

Reaction equation

HRID 2121322 reaction equation
C[O:2][C:3]([C:5]1([OH:28])[CH2:10][C@@H:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[C:8](=[CH2:19])[C@H:7]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:6]1)=O.C1COCC1>>[Si:12]([O:11][C@H:9]1[C:8](=[CH2:19])[C@H:7]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH2:6][C:5]([CH2:3][OH:2])([OH:28])[CH2:10]1)([C:15]([CH3:17])([CH3:18])[CH3:16])([CH3:14])[CH3:13]

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 10502782(3R,5R)-3,5-Bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy4-methylenecyclohexanecarboxylic Acid Methyl Ester

Product 1

HCID 10787320[(3R,5R)-3,5-Bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy4-methylenecyclohexyl]methanol

Procedure

(i) To a stirred solution of the ester 3 (90 mg, 0.21 mmol) in anhydrous THF (8 mL) lithium aluminum hydride (60 mg, 1.6 mmol) was added at 0° C. under argon. The cooling bath was removed after 1 h and the stirring was continued at 6° C. for 12 h and at room temperature for 6 h. The excess of the reagent was decomposed with saturated aq. Na2SO4, and the mixture was extracted with ethyl acetate and ether, dried (MgSO4) and evaporated. Flash chromatography of the residue with hexane/ethyl acetate (9:1) afforded unreacted substrate (12 mg) and a pure, crystalline diol 4 (35 mg, 48% based on recovered ester 3): 1H NMR (CDCl3+D2O) δ 0.079, 0.091, 0.100, and 0.121 (each 3H, each s, 4×SiCH3), 0.895 and 0.927 (9H and 9H, each s, 2×Si-t-Bu), 1.339 (1H, t, J ˜12 Hz), 1.510 (1H, dd, J=14.3, 2.7 Hz), 2.10 (2H, m), 3.29 and 3.40 (1H and 1H, each d, J=11.0 Hz), 4.66 (1H, t, J ˜2.8 Hz), 4.78 (1H, m), 4.92 (1H, t, J=1.7 Hz), 5.13 (1H, t, J=2.0 Hz); MS m/z (relative intensity) no M+, 345 (M+-t-Bu, 8), 327 (M+-t-Bu-H2O, 22), 213 (28), 195 (11), 73 (100).

Workup

  1. customThe cooling bath was removed after 1 h
  2. extractionthe mixture was extracted with ethyl acetate and ether
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customFlash chromatography of the residue with hexane/ethyl acetate (9:1) afforded unreacted substrate (12 mg)

Sources & evidence

ORD record
ord-a60b267ae2f243b7a7af45c090e3df97
Source dataset
uspto-grants-2004_02
Patent number
US06696431B2

Reaction notes

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