tert-Butyldimethylsilyl chloride → (4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

HRID 1807723Notes

Reaction equation

HRID 1807723 reaction equation
N12CCCN=C1CCCCC2.[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]([OH:43])([C:39]([F:42])([F:41])[F:40])[C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)=[O:20])=[CH:15][C:14]=1[F:44].[C:45]([Si:49]([CH3:52])([CH3:51])Cl)([CH3:48])([CH3:47])[CH3:46]>ClCCl>[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]([O:43][Si:49]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:52])[CH3:51])([C:35]([F:36])([F:37])[F:38])[C:39]([F:41])([F:42])[F:40])=[CH:30][CH:29]=3)[CH2:25][CH2:26]2)=[O:20])=[CH:15][C:14]=1[F:44]

Participants

5

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86638550(4-Amino-3-fluorophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanoneYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,8-Diazabicyclo[5.4.0]undec-7-ene (1.559 mmol, 0.233 mL, 237 mg) was added to a cooled (ice/slurry) solution of (4-amino-3-fluorophenyl)(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazin-1-yl)methanone (1.199 mmol, 575 mg) and tert-butyldimethylchlorosilane (1.559 mmol, 235 mg) in dichloromethane (20 mL) under nitrogen. The resulting solution was stirred for 15 minutes prior to the removal of the external cooling bath. The reaction was allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was diluted with dichloromethane (100 ml) and washed with 0.5M hydrochloric acid (100 ml), 0.5M sodium hydroxide (100 ml) and brine (100 ml). The organic phase was dried on magnesium sulfate, filtered and concentrated under vacuum to give a crude oil. This oil was purified by SCX chromatography to afford the title compound (534 mg). MS (ESI) m/z 594.3 [M+H]+

Workup

  1. customto the removal of the external cooling bath
  2. stirringstirred for 16 hours
  3. additionThe reaction mixture was diluted with dichloromethane (100 ml)
  4. washwashed with 0.5M hydrochloric acid (100 ml), 0.5M sodium hydroxide (100 ml) and brine (100 ml)
  5. customThe organic phase was dried on magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customto give a crude oil
  9. customThis oil was purified by SCX chromatography

Sources & evidence

ORD record
ord-f5af0375f4f148ae9a9558ed3e327c6a
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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