Ethyl Acetate → (R)-2-Bromo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanol

HRID 1351922Notes

Reaction equation

HRID 1351922 reaction equation
[Br:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:7]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:6]=1)=[O:4].C1(C2(C3C=CC=CC=3)OB(C)N3CCC[C@H]23)C=CC=CC=1.C(OCC)(=O)C.[Cl-].[NH4+]>O1CCCC1>[Br:1][CH2:2][C@@H:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:7]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:6]=1)[OH:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 9838490(R)-2-Methyl-CBS-oxazaborolidineHCID 11200351N-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]methanesulfonamide

Product 1

HCID 46938714(R)-2-Bromo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanolYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

Under nitrogen atmosphere, a solution of 2-bromo-1-[4-(phenyl-methoxy)-3-[(methylsulfonyl)amino]phenyl]ethanone (J. Med. Chem., vol. 23, no. 7, p. 738 (1980)) (977 mg, 2.45 mmol) and (R)-5,5-diphenyl-2-methyl-3,4-propano-1,3,2-oxazaborolidine (170 mg, 0.61 mmol) in tetrahydrofuran is stirred for 30 minutes. The mixture is cooled to −30° C., and thereto is added a 2M borane-dimethylsulfide complex in tetrahydrofuran (1.84 mL, 3.68 mmol), and the mixture is stirred at −25° C. for 2 days. The reaction solution is warmed to room temperature, and ethyl acetate and a saturated aqueous ammonium chloride solution are added thereto, and the mixture is stirred. The organic layer is collected and dried over anhydrous sodium sulfate. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (ethyl acetate/chloroform=1/50) to give the desired (R)-2-bromo-1-[4-(phenylmethoxy)-3-[(methylsulfonyl)-amino]phenyl]ethanol (881 mg, yield: 90%).

Workup

  1. temperatureThe reaction solution is warmed to room temperature
  2. stirringthe mixture is stirred
  3. customThe organic layer is collected
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent is evaporated under reduced pressure
  6. customthe residue is purified by silica gel column chromatography (ethyl acetate/chloroform=1/50)

Sources & evidence

ORD record
ord-e486a5828f774f639dc2795b2fa68c3a
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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