Sodium hydride → tert-Butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-oxopiperazine-1-carboxylate

HRID 1807780Notes

Reaction equation

HRID 1807780 reaction equation
[O:1]=[C:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1>CN1CCCC1=O.C(OCC)(=O)C>[F:27][C:26]([F:28])([F:29])[C:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:18][N:7]2[CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3][C:2]2=[O:1])=[CH:20][CH:21]=1)([OH:34])[C:30]([F:31])([F:33])[F:32]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 235273962-[4-(Bromomethyl)phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol

Product 1

HCID 86638570tert-Butyl 4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)-3-oxopiperazine-1-carboxylateYield 31.6%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirring solution of tert-butyl 3-oxopiperazine-1-carboxylate (9.99 mmol, 2 g) in dry N-methyl-2-pyrrolidinone (2 mL) was added sodium hydride (30.0 mmol, 1.198 g). The mixture was stirred at room temperature under nitrogen for 20 min before the addition of 2-(4-(bromomethyl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (10.99 mmol, 3.70 g). The mixture was stirred for a further 14 hours. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (4×75 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate concentrated. The resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—3.5% methanol/96.5% dichloromethane gradient) to afford the title compound (1.44 g).

Workup

  1. washwashed with water (4×75 mL)
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated
  5. customThe resulting residue was purified by column chromatography on silica gel (eluting with dichloromethane—3.5% methanol/96.5% dichloromethane gradient)

Sources & evidence

ORD record
ord-ab93eafb8d0e47a8ac3a79fed7a1bf93
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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