Sodium hydride → HCID 86705909, compound

HRID 339267Notes

Reaction equation

HRID 339267 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[H-].[Na+].Br[CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[Si:25]([O:24][CH2:23][CH2:22][O:1][CH2:2][C@@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2733675tert-butyl N-[(2S)-1-hydroxy-3-phenylpropan-2-yl]carbamateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilane

Product 1

HCID 86705909HCID 86705909, compoundYield 15.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of (S)-tert-butyl (1-hydroxy-3-phenylpropan-2-yl)carbamate (Alfa Aesar, 500 mg, 1.99 mmol) in DMF (13.0 mL) was added NaH (60% in mineral oil, 119 mg, 2.98 mmol). The resulting reaction mixture was stirred at 0° C. for 15 min and then (2-bromoethoxy)(tert-butyl)dimethylsilane (512 μL, 2.39 mmol) was added. The reaction mixture was stirred at 0° C. for 2 h and then at room temperature for 3 h. The mixture was poured into a separatory funnel containing EtOAc and sat. aq. NH4Cl. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. NaCl, dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified using flash chromatography (40 g column, gradient from 0% to 40% EtOAc/hexanes over 14 min) to give the title compound (124 mg, 15%) as a colorless oil. MS (ESI+) m/z 310.1 (M+H−Boc)+.

Workup

  1. customThe resulting reaction mixture
  2. stirringThe reaction mixture was stirred at 0° C. for 2 h
  3. waitat room temperature for 3 h
  4. additionThe mixture was poured into a separatory funnel
  5. extractionThe aqueous layer was extracted with EtOAc (3×)
  6. washthe combined organics were washed with sat. NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude oil was purified
  11. customflash chromatography (40 g column, gradient from 0% to 40% EtOAc/hexanes over 14 min)

Sources & evidence

ORD record
ord-e689340ce1f846b3a524b6cad651cbfb
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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