Benzyl Bromide → Benzyl (2S)-3-cyclobutyl-2-hydroxypropanoate

HRID 2301163Notes

Reaction equation

HRID 2301163 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].[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C=O)C>[OH:1][C@@H:2]([CH2:6][CH:7]1[CH2:10][CH2:9][CH2:8]1)[C:3]([O:5][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:4]

Participants

4

Reactant 2

HCID 7498Benzyl BromideHCID 21341063(S)-a-Hydroxy-cyclobutanepropanoic acid

Product 1

HCID 53678805Benzyl (2S)-3-cyclobutyl-2-hydroxypropanoateYield 70.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1.05 g (7.3 mmol) of 2-(S)-hydroxy-3-(cyclobutyl)propanoic acid (from Step D), 40 mL (10.0 mmol) of TEA and 1.20 mL (10.0 mmol) of benzyl bromide in 8 mL of DMF was stirred at rt for 2 h. The mixture was partitioned between 200 mL of ether and 100 mL of H2O and the layers were separated. The organic layer was washed with 100 mL of 2.0 N HCl, 100 mL of sat'd NaHCO3, 2×100 mL of H2O, 100 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 60 g of silica gel using 4:1 v/v hexanes/ether as the eluant afforded 1.20 g (70%) of the title compound: 1H NMR (500 MHz) δ 1.58-1.70 (m, 2H), 1.72-1.82 (m, 2H), 1.84-1.92 (m, 2H), 1.98-2.10 (m, 2H), 2.46-2.58 (m, 1H), 2.63 (br s, 1H), 4.15 (dd, J=7.5, 3.0), 7.33-7.40 (m, 5H).

Workup

  1. customThe mixture was partitioned between 200 mL of ether and 100 mL of H2O
  2. customthe layers were separated
  3. washThe organic layer was washed with 100 mL of 2.0 N HCl, 100 mL of sat'd NaHCO3, 2×100 mL of H2O, 100 mL of sat'd NaCl
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-72429462fb334238881ffc496ae4ea73
Source dataset
uspto-grants-2002_12
Patent number
US06498161B1

Reaction notes

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