(3-Bromopropoxy)(tert-butyl)dimethylsilane → HCID 67998721, compound

HRID 932165Notes

Reaction equation

HRID 932165 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH2:13]([C@@:16]1([CH3:42])[CH2:21][C@H:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[C@@H:19]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[N:18]([C@@H:36]([CH2:39][CH3:40])[CH:37]=[O:38])[C:17]1=[O:41])[CH:14]=[CH2:15]>C1COCC1.C(OCC)(=O)C>[CH2:13]([C@@:16]1([CH3:42])[CH2:21][C@H:20]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)[C@@H:19]([C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)[N:18]([C@H:36]([CH:37]([OH:38])[CH2:2][CH2:3][CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7])[CH2:39][CH3:40])[C:17]1=[O:41])[CH:14]=[CH2:15]

Participants

5

Reactant 2

HCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 58573909(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal

Product 1

HCID 67998721HCID 67998721, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

The Grignard reagent derived from of (3-bromopropoxy)(tert-butyl)dimethylsilane was prepared on 1.8 mmol scale according to Minguez, et al. Biorg. Med. Chem. 11, 3335, 2003 as a gray solution in THF (˜3 mL). About 1.5 mL of the Grignard regent was added slowly to a solution of (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal (100 mg, 0.22 mmol; Example 91, Step C) in THF (1 mL) at ambient temperature. After 2 h, the reaction was diluted in ethyl acetate and washed with saturated ammonium chloride solution followed by sat. aq. NaCl solution. The organic layer was dried over sodium sulfate and concentrated. Purification by silica chromatography eluting with ethyl acetate/hexane provided the title compound as a mixture of diastereomers.

Workup

  1. customwas prepared on 1.8 mmol scale
  2. washwashed with saturated ammonium chloride solution
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customPurification by silica chromatography
  6. washeluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-da25255927474a75a5018c5edc61c863
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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