Triethylamine → (R)-1-(2-chlorophenyl)ethyl (5-(4-bromophenyl)-3-methylisoxazol-4-yl)carbamate

HRID 553700Notes

Reaction equation

HRID 553700 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2C(O)=O)=[CH:4][CH:3]=1.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C@H:24]([OH:26])[CH3:25].C([N:29]([CH2:32]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:41])C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C@H:24]([O:26][C:32](=[O:41])[NH:29][C:9]1[C:10]([CH3:13])=[N:11][O:12][C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[CH3:25]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 6999092(1R)-1-(2-chlorophenyl)ethan-1-olHCID 566045595-(4-Bromophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid

Product 1

HCID 66660466(R)-1-(2-chlorophenyl)ethyl (5-(4-bromophenyl)-3-methylisoxazol-4-yl)carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

5-(4-Bromo-phenyl)-3-methyl-isoxazole-4-carboxylic acid (10 g, 35 mmol), (R)-1-(2-chloro-phenyl)-ethanol (6.6 g, 42 mmol), triethylamine (10 mL, 70 mmol), and diphenylphosphoryl azide (11.5 g, 42 mmol) were combined in toluene (100 mL) and stirred at 90° C. for 1 hour. The mixture was concentrated, and the residue was purified by silica gel chromatography (0-30% EtOAc in hexanes). The isolated product was recrystallized in 5:1 hexanes:acetone to give the title compound in >99% e.e (by chiral HPLC. Chiracel OD 98.4% hexanes/1.6% Ethanol. Major isomer 27.9 min minor isomer 32.7 min).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by silica gel chromatography (0-30% EtOAc in hexanes)
  3. customThe isolated product was recrystallized in 5:1 hexanes

Sources & evidence

ORD record
ord-6c9e9d7b5858467c9a364fba2dd99b2d
Source dataset
uspto-grants-2011_11
Patent number
US08048902B2

Reaction notes

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