Sodium cyanoborohydride → (3RS,4RS)-4-[8-(t-Butyldimethylsilyloxy)-1-octyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman

HRID 1792349Notes

Reaction equation

HRID 1792349 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[C:16][C:17]1(O)[C:26]2[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=2)[S:20][CH2:19][C:18]1([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=1)[CH3:29])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([BH3-])#N.[Na+]>ClCCCl>[Si:1]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]1[C:26]2[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=2)[S:20][CH2:19][C:18]1([C:30]1[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=1)[CH3:29])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 220330184-[8-(t-Butyldimethylsilyloxy)-1-octynyl]-4-hydroxy-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman

Product 1

HCID 22033292(3RS,4RS)-4-[8-(t-Butyldimethylsilyloxy)-1-octyl]-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochromanYield 80.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-[8-(t-Butyldimethylsilyloxy)-1-octynyl]-4-hydroxy-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman (14 g, 25.2 mmol) was dissolved in 1,2-dichloroethane (300 mL) and cooled to 0° C. Zinc iodide(II) (24.2 g, 75.69 mmol) and sodium cyanoborohydride (9.51 g, 151.38 mmol) was sequentially added and slowly warmed to room temperature and stirred for 2 hours. After the reaction was completed, the reaction solvent was removed under reduced pressure. The residue was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and removed by evaporation under vacuum. This product was purified by column chromatography on silica gel, eluting with 10% ethyl acetate in n-hexane. After removal of the solvent, crude 11 g of the title compound was obtained as pale yellow oil. (yield: 79.5%) Then, this compound thus obtained (11 g) was dissolved in tetrahydrofuran (300 mL). 0.2N NaHCO3(300 mL) and 10% palladium on carbon (3 g) was added and stirred for 2 day under hydrogen (atmospheric pressure). The reaction mixture was filtered through cellite and concentrated under reduced pressure. The residue was dissolved in ethyl acetate, which was washed with water and brine. The organic solvent was dried over anhydrous magnesium sulfate and removed by evaporation under vacuum. This product was purified by column chromatography on silica gel, eluting with ethyl acetate:n-hexane=1:40. After removal of the solvent, 5.6 g of the title compound was obtained as colorless oil. (yield: 50.5%).

Workup

  1. temperatureslowly warmed to room temperature
  2. customthe reaction solvent was removed under reduced pressure
  3. additionThe residue was poured into water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customremoved by evaporation under vacuum
  7. customThis product was purified by column chromatography on silica gel
  8. washeluting with 10% ethyl acetate in n-hexane
  9. customAfter removal of the solvent

Sources & evidence

ORD record
ord-a8f3a55a43a74e6ba428e2e64d7b4e5d
Source dataset
uspto-grants-2006_07
Patent number
US07074819B2

Reaction notes

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