Sodium hydride → 2-[2-(5-Bromo-2-fluoro-phenyl)-3,3-difluoro-2-(2-nitro-benzenesulfonylamino)-propoxy]-2-methyl-propionic acid tert-butyl ester

HRID 221744Notes

Reaction equation

HRID 221744 reaction equation
[OH:1][C:2]([CH3:11])([CH3:10])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].[Br:14][C:15]1[CH:16]=[CH:17][C:18]([F:39])=[C:19]([C:21]2([CH:36]([F:38])[F:37])[CH2:23][N:22]2[S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])[CH:20]=1>CN(C=O)C.C1COCC1>[C:6]([O:5][C:3](=[O:4])[C:2]([O:1][CH2:23][C:21]([C:19]1[CH:20]=[C:15]([Br:14])[CH:16]=[CH:17][C:18]=1[F:39])([NH:22][S:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])[CH:36]([F:38])[F:37])([CH3:11])[CH3:10])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 118940tert-Butyl 2-hydroxyisobutyrateHCID 866502672-(5-Bromo-2-fluorophenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine

Product 1

HCID 666658022-[2-(5-Bromo-2-fluoro-phenyl)-3,3-difluoro-2-(2-nitro-benzenesulfonylamino)-propoxy]-2-methyl-propionic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl α-hydroxyisobutyrate (533 mg, 3.32 mmol) in 4.5 mL DMF and 0.75 mL THF was added portion wise (133 mg, 3.32 mmol) sodium hydride at room temperature. After the reaction mixture had been stirring for 15 minutes, a solution of 2-(5-bromo-2-fluoro-phenyl)-2-difluoromethyl-1-(2-nitro-benzenesulfonyl)-aziridine (1 g, 2.22 mmol) was added. The reaction mixture was stirred at rt for 150 minutes and quenched with aqueous NH4Cl solution. TBME was added, the layers were separated, washed with brine and TBME. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 6/1->5/1 to give 1.10 g of the title compound as a pale yellow resin.

Workup

  1. stirringThe reaction mixture was stirred at rt for 150 minutes
  2. customquenched with aqueous NH4Cl solution
  3. additionTBME was added
  4. customthe layers were separated
  5. washwashed with brine and TBME
  6. dry with materialThe combined organic layers were dried over MgSO4.H2O
  7. customevaporated
  8. customThe crude product was purified on a silica gel column
  9. washby eluting with hexane/EtOAc 6/

Sources & evidence

ORD record
ord-750ac4c55b2a4d9abc15ba1c61a1f264
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

Loading…