3,5-Bis(trifluoromethyl)benzyl bromide → HCID 86602049, compound

HRID 1295364Notes

Reaction equation

HRID 1295364 reaction equation
[CH2:1]([N:8]1[CH2:13][CH:12]2[C@:10]([OH:14])([CH2:11]2)[C@@H:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:32][C:33]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[C:35]([C:43]([F:46])([F:45])[F:44])[CH:34]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[CH2:1]([N:8]1[CH2:13][CH:12]2[C@:10]([O:14][CH2:32][C:33]3[CH:34]=[C:35]([C:43]([F:45])([F:46])[F:44])[CH:36]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:38]=3)([CH2:11]2)[C@@H:9]1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 69335514HCID 69335514, compound

Product 1

HCID 86602049HCID 86602049, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To Intermediate 28, mixture of diastereomers ((1R,2S)-3-benzyl-2-phenyl-3-aza-bicyclo[3.1.0]hexan-1-ol (0.40 g, 1.5 mmol) and tetrabutylammonium iodide (0.26 g, 0.70 mmol) in a flask was added THF (15 mL) and the mixture cooled to −78° C. Potassium bis(trimethylsilyl)amide (0.5M/toluene, 4.5 mL, 2.2 mmol) was added dropwise and the reaction was stirred for 10 minutes. 1-Bromomethyl-3,5-bis-trifluoromethyl-benzene (0.39 mL, 2.1 mmol) was added dropwise and the reaction stirred for an additional 10 minutes, then allowed to warm to room temperature. The solvent was removed at reduced pressure and the residue partitioned between H2O and EtOAc, the organics washed with brine and dried over calcium sulfate, filtered and concentrated. The crude product was purified on a Biotage flash 40 system eluted with a gradient of 1% ETOAc/Hexanes to 2% ETOAc/Hexanes to give the title compound as an oil. (0.55 g, 74% yield).

Workup

  1. stirringthe reaction stirred for an additional 10 minutes
  2. temperatureto warm to room temperature
  3. customThe solvent was removed at reduced pressure
  4. customthe residue partitioned between H2O and EtOAc
  5. washthe organics washed with brine
  6. dry with materialdried over calcium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified on a Biotage flash 40 system
  10. washeluted with a gradient of 1% ETOAc/Hexanes to 2% ETOAc/Hexanes

Sources & evidence

ORD record
ord-26fc018340f14058aaeb34effed06389
Source dataset
uspto-grants-2007_07
Patent number
US07241798B2

Reaction notes

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