4-Chlorobenzaldehyde → (S)-4-[3-(4-chloro-phenyl)-3-hydroxy-prop-1-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 885193Notes

Reaction equation

HRID 885193 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]#[CH:14])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1>C1COCC1.CCCCCC>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]#[C:14][CH:27]([C:26]2[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=2)[OH:28])[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 11160457tert-Butyl (4S)-4-ethynyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylateHCID 178418339Butyllithium

Product 1

HCID 59173103(S)-4-[3-(4-chloro-phenyl)-3-hydroxy-prop-1-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a stirred solution of (S)-4-ethynyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (3.16 g; CAS 173065-16-2) in dry THF (20 ml) under an argon atmosphere at −78° C. was added dropwise a solution of n-butyllithium in hexane (10.5 ml, 1.6 M solution) and stirring continued for 30 min. A solution of 4-chlorobenzaldehyde (2.17 g) in THF (10 ml) was added dropwise and the mixture was stirred for a further 2 h at −78° C. The reaction mixture was then quenched by careful addition of water (12 ml) and allowed to warm to room temperature. The mixture was diluted with ethyl acetate and washed with saturated brine. The combined organic phase was dried over sodium sulphate, filtered and concentrated in vacuo. The reside was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S)-4-[3-(4-chloro-phenyl)-3-hydroxy-prop-1-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (mixture of epimers) as a yellow oil. MS (ISP): 426.1 ([{37Cl}M+OAc]−), 424.1 ([{35Cl}M+OAc]−).

Workup

  1. stirringthe mixture was stirred for a further 2 h at −78° C
  2. customThe reaction mixture was then quenched by careful addition of water (12 ml)
  3. additionThe mixture was diluted with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialThe combined organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe reside was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-638a85d1be1742c085fc60b96282322c
Source dataset
uspto-grants-2012_08
Patent number
US08242153B2

Reaction notes

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