Chlorotrimethylsilane → HCID 54398754, compound

HRID 1533264Notes

Reaction equation

HRID 1533264 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][C:24]([O:26][CH3:27])=[O:25])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl[Si:29]([CH3:32])([CH3:31])[CH3:30]>O1CCCC1.CCCCCC>[CH2:9]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]=[C:24]([O:26][CH3:27])[O:25][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 2724682Lithium diisopropylamideHCID 11076055Methyl 2-(2-(benzyloxy)phenyl)acetate

Product 1

HCID 54398754HCID 54398754, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Procedure

To a dry ice-acetone bath cooled 1.45M solution of lithium diisopropylamide in a mixture of tetrahydrofuran and n-hexane (1.4 ml) was added methyl (2-benzyloxyphenyl)acetate (256 mg). The mixture was stirred for 30 minutes at the same temperature and then for 30 minutes at 0° C. After cooling the solution to −78° C. chlorotrimethylsilane (0.3 ml) was added and the mixture was allowed to warm to room temperature. The solution was diluted with n-hexane (50 ml), filtered through celite, and concentrated under reduced pressure to afford 2-(2-benzyloxyphenyl)-1-methoxy-1-trimethylsilyloxyethylene. To an ice bath cooled solution of (2S)-3-methyl-2-(p-tolylsulfonylamino)butanol (288 mg) in dichloromethane (10 ml) was added a 1M solution of borane-tetrahydrofuran complex in tetrahydrofuran (1.0 ml) and the mixture was stirred for 30 minutes at ambient temperature. After cooling the solution to −78° C., cyclohexanecarbaldehyde (112 mg) and a solution of 2-(2-benzyloxyphenyl)-1-methoxy-1-trimethylsilyloxyethylene prepared above in dichloromethane (1 ml) were added. The solution was stirred for one hour at −78° C. and then quenched by an aqueous solution of sodium bicarbonate at 0° C. The mixture was extracted with diethyl ether, dried and evaporated in vacuo. The residue was dissolved in a mixture of tetrahydrofuran (4 ml) and aqueous 1M solution of hydrochloric acid (2 ml), and the resulting solution was allowed to stand for 30 minutes. Aqueous solution of sodium bicarbonate was added thereto and the mixture was extracted with ether. The organic layer was dried and evaporated. Preparative thin layer chromatography [silica gel, ether - hexane (1:4)] afforded methyl (2R,3R)-2-(2-benzyloxyphenyl)-3-cyclohexyl-3-hydroxypropionate (187 mg). High pressure liquid chromatography analysis (Daicel AD column eluting with 20% isopropyl alcohol - hexane) indicated an enantiomeric excess of 95% (Rt: major 10.51 minutes, minor 8.60 minutes).

Workup

  1. waitfor 30 minutes at 0° C
  2. additionwas added
  3. filtrationfiltered through celite
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-85dcf0041a294a50916718c277477f33
Source dataset
uspto-grants-2001_03
Patent number
US06207686B1

Reaction notes

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