4-Methyloxybenzyl chloride → 4-(Methoxy)benzyl 2-(S)-hydroxy-3-(cyclobutyl)propanoate

HRID 1386686Notes

Reaction equation

HRID 1386686 reaction equation
[OH:1][C@@H:2]([CH2:6][CH:7]1[CH2:10][CH2:9][CH2:8]1)[C:3]([OH:5])=[O:4].[CH3:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17]Cl)=[CH:15][CH:14]=1>>[OH:1][C@@H:2]([CH2:6][CH:7]1[CH2:10][CH2:9][CH2:8]1)[C:3]([O:5][CH2:17][C:16]1[CH:19]=[CH:20][C:13]([O:12][CH3:11])=[CH:14][CH:15]=1)=[O:4]

Participants

3

Reactant 2

HCID 699934-Methyloxybenzyl chlorideHCID 21341063(S)-a-Hydroxy-cyclobutanepropanoic acid

Product 1

HCID 206724394-(Methoxy)benzyl 2-(S)-hydroxy-3-(cyclobutyl)propanoateYield 75%

Procedure

A mixture of 432 mg (3.0 mmol) of 2-(S)-hydroxy-3-cyclobutyl propanoic acid (from EXAMPLE 19, Step D), 0.61 mL of 4-(methoxy)benzyl chloride and 0.63 mL of TEA was stirred at rt for 20 h. The reaction mixture was partitioned between 100 mL of ether and 50 mL of H2O and the layers were separated. The organic layer was washed with 50 mL of sat'd NaHCO3, 50 mL of 2.0 N HCl, 2×50 mL of H2O and 50 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 30 g of silica gel using 4:1 v/v hexanes/ether as the eluant afforded 598 mg (75%) of the title compound: 1H NMR (500 MHz) δ 1.56-1.94 (6H), 1.98-2.12 (m, 2H), 2.44-2.56 (m, 1H),2.64 (br s, 1H), 3.82 (s, 3H), 4.11-4.13 (m, 1H), 5.19 (ABq, J=25.0, 2H), 6.90 (d, J=9.0, 2H), 7.30 (d, J=9.0, 2H).

Workup

  1. customThe reaction mixture was partitioned between 100 mL of ether and 50 mL of H2O
  2. customthe layers were separated
  3. washThe organic layer was washed with 50 mL of sat'd NaHCO3, 50 mL of 2.0 N HCl, 2×50 mL of H2O and 50 mL of sat'd NaCl
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8b5ed650001d432c8e6a8d4229e91b37
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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