Diethyl Ether → (r/s)-3-Cyclohexyl-2-hydroxy-propanoic acid, 4-(methoxy)benzyl ester

HRID 1386682Notes

Reaction equation

HRID 1386682 reaction equation
CO[C:3]1[CH:14]=[CH:13][C:6]([CH2:7][C:8](=[O:12])[C:9]([O-:11])=[O:10])=[CH:5][CH:4]=1.[CH:15]1([CH2:21][Mg]Br)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.BrCC1CCCCC1.BrCCBr.C[CH2:37][O:38]CC>C1(C)C=CC=CC=1>[CH:6]1([CH2:7][CH:8]([OH:12])[C:9]([O:11][CH2:21][C:15]2[CH:20]=[CH:19][C:18]([O:38][CH3:37])=[CH:17][CH:16]=2)=[O:10])[CH2:5][CH2:4][CH2:3][CH2:14][CH2:13]1

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 78391,2-DibromoethaneHCID 137636Cyclohexane, (bromomethyl)-HCID 19878614-(Methoxy)benzylglyoxylateHCID 178419664HCID 178419664, compound

Product 1

HCID 76635352(r/s)-3-Cyclohexyl-2-hydroxy-propanoic acid, 4-(methoxy)benzyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 0.50 g (2.32 mmol) of 4-(methoxy)benzylglyoxylate (azeotropically dried with 2×25 mL of toluene) in 2 mL of ether at −78° C. was treated with 7 mL of 0.5 M of cyclohexylmethylmagnesium bromide (prepared from 1.0 mL (7.1 mmol) of bromomethylcyclohexane, 174 mg (7.1 mmol) of Mg, 0.1 mL (1.1 mmol) of 1,2-dibromoethane in 14 mL of ether) and the resulting mixture was stirred cold for 1 h. The reaction was quenched with 1 N NaHCO3 and the quenched mixture was partitioned between 100 mL of ether and 100 mL of sat'd NaHCO3. The aqueous layer was separated and extracted with 100 mL of ether. The combined organic layers were dried over MgSO4 and concentrated. Flash chromatography on silica gel using 4:1 v/v hexanes/EtOAc afforded 180 mg (26%) of the title compound: RF: 0.32 (4:1 v/v hexanes/EtOAc); 1H NMR (300 MHz) δ 0.84-1.82 (m, 13H), 3.81 (s, 3H), 4.23 (m, 1H), 5.14 (s, 2H), 6.90 (d, J=8.7, 2H), 7.29 (d, J=8.7, 2H).

Workup

  1. customThe reaction was quenched with 1 N NaHCO3
  2. customthe quenched mixture was partitioned between 100 mL of ether and 100 mL of sat'd NaHCO3
  3. customThe aqueous layer was separated
  4. extractionextracted with 100 mL of ether
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1e05096631594779aeed257b97c17257
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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