Imidazole → 2-((3S)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutyl)-6-methoxyphenol

HRID 433144Notes

Reaction equation

HRID 433144 reaction equation
C([O:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:17][CH2:18][C@H:19]([OH:22])[CH2:20][OH:21])C1C=CC=CC=1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24].N1C=CN=C1>CN(C)C=O.O.C(OCC)(=O)C.C(O)C.[Pd]>[Si:23]([O:21][CH2:20][C@@H:19]([OH:22])[CH2:18][CH2:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[OH:8])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

9

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11335655(2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediol

Product 1

HCID 114161542-((3S)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutyl)-6-methoxyphenolYield 85%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediol (8.00 g, 26.5 mmol) in N,N-dimethylformamide (250 mL) cooled to 0° C. was added tert-butyldimethylsilyl chloride (4.39 g, 29.1 mmol) followed by imidazole (2.16 g, 31.8 mmol) and the reaction mixture was allowed to stir at room temperature for 4 h. The reaction mixture was diluted with water (500 mL) and ethyl acetate (200 mL). The aqueous phase was separated and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with aqueous hydrogen chloride (200 mL), water (4×200 mL), aqueous sodium chloride (300 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. The residue was dissolved in ethanol (300 mL), palladium on carbon (10 wt. %, 1.00 g) was added, and the reaction mixture was shaken under an H2 atmosphere (50 psi) for 6 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:4) gave 7.33 g (85%, 40% ee) of 2-((3S)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxybutyl)-6-methoxyphenol as a colorless oil which crystallized upon standing. Rf=0.53 (silica, ethyl acetate:hexanes 1:4); mp 44-46° C.; Anal. Calcd. for C17H30O4Si: C, 62.54; H, 9.26. Found: C, 62.41; H, 9.19.

Workup

  1. customThe aqueous phase was separated
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. washThe combined organic extracts were washed with aqueous hydrogen chloride (200 mL), water (4×200 mL), aqueous sodium chloride (300 mL)
  4. dry with materialdried (magnesium sulfate)
  5. customthe solvent was removed in vacuo
  6. customto give a crude oil
  7. stirringthe reaction mixture was shaken under an H2 atmosphere (50 psi) for 6 h
  8. filtrationThe reaction mixture was filtered (celite)
  9. customthe solvent removed in vacuo
  10. customto provide a crude oil
  11. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 1:4)

Sources & evidence

ORD record
ord-c70e0b14a522404ea3a637c0bf70beec
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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