Diisopropylamine → methyl (2RS,3RS)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate

HRID 1533254Notes

Reaction equation

HRID 1533254 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27][C:28]([O:30][CH3:31])=[O:29])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:32]1([CH:38]=[O:39])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>O1CCCC1.CCCCCC>[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH:27]([CH:38]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[OH:39])[C:28]([O:30][CH3:31])=[O:29])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 16275CyclohexanecarboxaldehydeHCID 11076055Methyl 2-(2-(benzyloxy)phenyl)acetateHCID 178418339Butyllithium

Product 1

HCID 86756555methyl (2RS,3RS)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionateYield 36.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a dry ice-acetone bath cooled solution of diisopropylamine (4.84 g) in tetrahydrofuran (100 ml) was added a 1.61M solution of n-butyl lithium in n-hexane (24.8 ml) and the mixture was stirred for 30 minutes at the same temperature. Methyl (2-benzyloxyphenyl)acetate (5.12 g) was added and the mixture was stirred at −70° C. for 30 minutes and allowed to warm to 0° C. Cyclohexanecarbaldehyde (2.24 g) was added and the solution was stirred for 30 minutes. The reaction mixture was quenched by 1N aqueous hydrochloric acid solution (80 ml), washed with aqueous sodium bicarbonate solution and brine, dried, and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluting with 20% diethyl ether in hexane) to afford less polar isomer of methyl (2RS,3SR)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate (isomer A) (394 mg) and more polar isomer of methyl (2RS,3RS)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate (isomer B) (2.67 g).

Workup

  1. stirringthe mixture was stirred at −70° C. for 30 minutes
  2. stirringthe solution was stirred for 30 minutes
  3. customThe reaction mixture was quenched by 1N aqueous hydrochloric acid solution (80 ml)
  4. washwashed with aqueous sodium bicarbonate solution and brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography on silica gel (eluting with 20% diethyl ether in hexane)

Sources & evidence

ORD record
ord-dbea31837c4940f899aa86f7e7207063
Source dataset
uspto-grants-2001_03
Patent number
US06207686B1

Reaction notes

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