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

HRID 1805222Notes

Reaction equation

HRID 1805222 reaction equation
[I: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]([I: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 582563541-(4-Iodophenyl)cyclopropanecarbaldehydeHCID 59173188(R)-4-(benzothiazole-2-sulfonylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67151684(S)-4-{(Z)-2-[1-(4-iodo-phenyl)-cyclopropyl]-vinyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl esterYield 72.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred, cooled (0° C.) solution of 1-(4-iodo-phenyl)-cyclopropanecarbaldehyde (1.6 g) in tetrahydrofurane (40 ml) was added under an argon atmosphere (R)-4-(benzothiazole-2-sulfonylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (2.9 g) [CAS 1043499-96-2] followed by a 1 M solution of LiHMDS in THF (11.8 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 (50 ml) and H2O (50 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-iodo-phenyl)-cyclopropyl]-vinyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (2.0 g) as light yellow solid. MS (ISP): 470.3 ([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 (50 ml) and H2O (50 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-95c2be060b18479c80bf52e50557deb1
Source dataset
uspto-grants-2013_01
Patent number
US08354441B2

Reaction notes

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