Cyclohexanecarboxaldehyde → Methyl (2RS,3SR)-2-(2-benzyloxyphenylmethyl)-3-cyclohexyl-3-hydroxypropionate

HRID 1533249Notes

Reaction equation

HRID 1533249 reaction equation
[CH:1]([N-]C(C)C)(C)C.[Li+].[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][C:25]([O-:27])=[O:26])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH:28]1([CH:34]=[O:35])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>O1CCCC1>[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH:24]([CH:34]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)[OH:35])[C:25]([O:27][CH3:1])=[O:26])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 16275CyclohexanecarboxaldehydeHCID 2724682Lithium diisopropylamideHCID 220124463-(2-Benzyloxyphenyl)propionate

Product 1

HCID 86756554Methyl (2RS,3SR)-2-(2-benzyloxyphenylmethyl)-3-cyclohexyl-3-hydroxypropionate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of lithium diisopropylamide (1.55M in n-hexane) in tetrahydrofuran (2 ml) was added a solution of 3-(2-benzyloxyphenyl)propionate (140 mg) in tetrahydrofuran (1.4 ml) and the mixture was stirred for 30 minutes. Cyclohexanecarbaldehyde (80 mg) was added. After being stirred for 30 minutes at the same temperature, the mixture was quenched by 1N hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with diethyl ether. The combined organic layer was washed with aqueous sodium bicarbonate solution and brine successively, dried and evaporated under reduced pressure. The residue was purified by preparative thin layer chromatography (silica gel, 60% diethyl ether - hexane) to afford less polar isomer of methyl (2RS,3SR)-2-(2-benzyloxyphenylmethyl)-3-cyclohexyl-3-hydroxypropionate (isomer A) (56.2 mg) and more polar isomer of methyl (2RS,3RS)-2-(2-benzyloxyphenylmethyl)-3-cyclohexyl-3-hydroxypropionate (isomer B) (74.4 mg).

Workup

  1. stirringAfter being stirred for 30 minutes at the same temperature
  2. customthe mixture was quenched by 1N hydrochloric acid
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with diethyl ether
  5. washThe combined organic layer was washed with aqueous sodium bicarbonate solution and brine successively
  6. customdried
  7. customevaporated under reduced pressure
  8. customThe residue was purified by preparative thin layer chromatography (silica gel, 60% diethyl ether - hexane)

Sources & evidence

ORD record
ord-3cec13cd6d164b1b927d17fc47a0a422
Source dataset
uspto-grants-2001_03
Patent number
US06207686B1

Reaction notes

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