Lithium Hexamethyldisilazide → (S)-4-{(Z)-2-[1-(4-chloro-phenyl)-cyclopropyl]-vinyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1026128Notes

Reaction equation

HRID 1026128 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:11]=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:13]([O:17][C:18]([N:20]1[C@@H:24]([CH2:25]S(C2SC3C=CC=CC=3N=2)(=O)=O)[CH2:23][O:22][C:21]1([CH3:39])[CH3:38])=[O:19])([CH3:16])([CH3:15])[CH3:14].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>O1CCCC1>[C:13]([O:17][C:18]([N:20]1[C@@H:24](/[CH:25]=[CH:11]\[C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10]2)[CH2:23][O:22][C:21]1([CH3:38])[CH3:39])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 114694361-(4-Chlorophenyl)cyclopropanecarbaldehydeHCID 59173188(R)-4-(benzothiazole-2-sulfonylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67178365(S)-4-{(Z)-2-[1-(4-chloro-phenyl)-cyclopropyl]-vinyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl esterYield 95.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred, cooled (0° C.) solution of 1-(4-chloro-phenyl)-cyclopropanecarbaldehyde (0.36 g) in tetrahydrofuran (15 ml) was added under an argon atmosphere (R)-4-(benzothiazole-2-sulfonylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.0 g) followed by a 1 M solution of LiHMDS in THF (4.8 ml). After 1 h at 0° C. the cooling bath was removed and stirring was continued overnight. The mixture was quenched by the addition of sat. aqueous NH4Cl (15 ml) and H2O (15 ml) and extracted with EtOAc. The aqueous phase was back extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (SiO2; gradient: heptane ->heptane/EtOAc 2:1) to give (S)-4-{(Z)-2-[1-(4-chloro-phenyl)-cyclopropyl]-vinyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (0.72 g) as light yellow viscous oil. MS (ISP): 378.3 ([M+H]+))

Workup

  1. customAfter 1 h at 0° C. the cooling bath was removed
  2. customThe mixture was quenched by the addition of sat. aqueous NH4Cl (15 ml) and H2O (15 ml)
  3. extractionextracted with EtOAc
  4. extractionThe aqueous phase was back extracted with EtOAc
  5. washThe combined organics were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (SiO2; gradient: heptane ->heptane/EtOAc 2:1)

Sources & evidence

ORD record
ord-a9c112b5169e489383659753c1b417e2
Source dataset
uspto-grants-2014_05
Patent number
US08729113B2

Reaction notes

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