HCID 86653293, compound → HCID 67151607, compound

HRID 1805254Notes

Reaction equation

HRID 1805254 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]([CH:18]=[O:19])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:21][Mg]Br>C1COCC1.CCOCC>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]([CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=1)[CH:18]([OH:19])[CH3:21])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 86653293HCID 86653293, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67151607HCID 67151607, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred, cooled solution of [(S)-3-(4-bromo-phenyl)-1-formyl-propyl]-carbamic acid tert-butyl ester (7.3 g) in THF (40 ml) and Et2O (30 ml) at 0° C. was added dropwise over 30 min a solution of methylmagnesium bromide (20.0 ml, 3 M solution in Et2O). The reaction mixture was then stirred at room temperature for 4 hours before being quenched by dropwise addition of water (gas formation!). The reaction mixture was then poured into EtOAc, the layers were separated and the organic layer was washed sequentially with diluted aq. HCl (pH 5) and saturated brine, then dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, gradient: 0% to 80% EtOAc in hexane) to afford {(1S,2RS)-1-[2-(4-bromo-phenyl)-ethyl]-2-hydroxy-propyl}-carbamic acid tert-butyl ester as a colourless amorphous solid comprising a mixture of epimers (5.1 g, 66%). MS (EI): 303 ([{81Br}M-C4H8]+), 301 ([{79Br} M-C4H8]+), 258([{81Br}M-C4H8—CO2H]+), 256 ([{79Br} M-C4H8—CO2H]+), 214, 212, 171, 169, 57 ([C4H9]+).

Workup

  1. custombefore being quenched by dropwise addition of water (gas formation!)
  2. additionThe reaction mixture was then poured into EtOAc
  3. customthe layers were separated
  4. washthe organic layer was washed sequentially with diluted aq. HCl (pH 5) and saturated brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (silica gel, gradient: 0% to 80% EtOAc in hexane)

Sources & evidence

ORD record
ord-f8d8cfdfc6094c7f80a2a81d41a519f1
Source dataset
uspto-grants-2013_01
Patent number
US08354441B2

Reaction notes

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