2-(Benzyloxy)-1-(3-butenyl)-3-methoxybenzene → (2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediol

HRID 433135Notes

Reaction equation

HRID 433135 reaction equation
CC[C@H]1[C@H]2C[C@H]([C@H](OC3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:28]([O:35][C@H:36]([C:47]4[CH:56]=[CH:55]N=C5[C:48]=4[CH:49]=[C:50]([O:57]C)[CH:51]=C5)[C@@H:37]4N5C[C@H](CC)[C@@H](CC5)[CH2:38]4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.[CH2:59]([O:66]C1C(OC)=CC=CC=1CCC=C)C1C=CC=CC=1.O.C([OH:84])(C)(C)C>>[CH2:28]([O:35][C:36]1[C:37]([O:66][CH3:59])=[CH:38][CH:55]=[CH:56][C:47]=1[CH2:48][CH2:49][C@H:50]([OH:57])[CH2:51][OH:84])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

4

Reactant 3

HCID 121149552-(Benzyloxy)-1-(3-butenyl)-3-methoxybenzeneHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineHCID 714019492-Methylpropan-2-ol--water (1/1)2×

Product 1

HCID 11335655(2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediolYield 92%

Conditions

Temperature
0 °C

Procedure

To a suspension of AD-mix-α (63.28 g) in water:tert-butyl alcohol (1:1, 300 mL) cooled to 0° C. was slowly added via an addition funnel to a solution of 2-(benzyloxy)-1-(3-butenyl)-3-methoxybenzene (12.13 g, 45.2 mmol) in water:tert-butyl alcohol (1:1, 300 mL) and the reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was quenched by the addition of sodium sulfite. The reaction mixture was diluted with water (500 mL) and ethyl acetate (500 mL). The aqueous phase was separated and extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 4:1) gave 12.57 g (92%, 40% ee) of (2S)-4-[2-(benzyloxy)-3-methoxyphenyl]-1,2-butanediol as a colorless oil. [α]D25=−3.04 (c 10.2 in methanol, 40% ee); Rf=0.72 (silica, ethyl acetate:hexanes 4:1); Anal. Calcd. for C18H22O4.0.1 H2O: C, 71.08; H, 7.36. Found: C, 70.95; H, 7.33.

Workup

  1. customThe reaction mixture was quenched by the addition of sodium sulfite
  2. additionThe reaction mixture was diluted with water (500 mL) and ethyl acetate (500 mL)
  3. customThe aqueous phase was separated
  4. extractionextracted with ethyl acetate (2×200 mL)
  5. washThe combined organic extracts were washed with aqueous sodium chloride (400 mL)
  6. dry with materialdried (magnesium sulfate)
  7. customthe solvent was removed in vacuo
  8. customto give a crude oil
  9. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 4:1)

Sources & evidence

ORD record
ord-99f18b887a1249e197851bdb5801ee65
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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