Boron trifluoride etherate → 2-[2-Azido-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

HRID 2196254

Reaction equation

HRID 2196254 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]([O:10][CH2:11][C:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Br:21])[CH:16]=1)(O)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6].C[Si]([N:27]=[N+:28]=[N-:29])(C)C.B(F)(F)F.CCOCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:22])[C:4]([O:10][CH2:11][C:12]([N:27]=[N+:28]=[N-:29])([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Br:21])[CH:16]=1)[CH3:13])([CH3:9])[C:5]([F:8])([F:7])[F:6]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 78378AzidotrimethylsilaneHCID 666655182-[2-(3-Bromo-phenyl)-2-hydroxy-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

Product 1

HCID 866502592-[2-Azido-2-(3-bromo-phenyl)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-[2-(3-bromo-phenyl)-2-hydroxy-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid methyl ester (5.1 g, 11.92 mmol) in toluene (50 ml) was added trimethylsilyl azide (3.95 ml, 29.8 mmol) and at 0° C. BF3-Et2O (4.53 ml, 35.8 mmol). The reaction mixture was stirred for 2 days at 25° C. and for another day at 40° C. The reaction was carefully quenched by slow addition of the reaction mixture to a cold aqueous NH4OH solution. The product was extracted with EtOAc and the combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated. The crude product was purified by flash-chromatography on silica gel (toluene to toluene/EtOAc 10:1) to provide a diastereomeric mixture of the title compound as a light yellow oil: TLC (toluene/EtOAc 10:1): Rf=0.69; HPLC RtH5=1.560 min; 1H NMR (360 MHz, CDCl3): δ 7.65 (s, 1H), 7.48 (d, 1H), 7.41 (d, 1H), 7.27 (t, 1H), 3.87 and 3.85 (s, 3H), 3.76 (m, 2H), 1.78 and 1.75 (s, 3H), 1.65 and 1.61 (s, 3H); ESIMS: 427, 429 [(M+NH4)+].

Workup

  1. customat 0° C
  2. customThe reaction was carefully quenched by slow addition of the reaction mixture to a cold aqueous NH4OH solution
  3. extractionThe product was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash-chromatography on silica gel (toluene to toluene/EtOAc 10:1)
  9. customto provide

Sources & evidence

ORD record
ord-bf91497a7aac476cb03be7eacdf8312d
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Linked notes

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