Sodium hydride → (R)-2-[2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

HRID 474064Notes

Reaction equation

HRID 474064 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C@:5]([OH:11])([CH3:10])[C:6]([F:9])([F:8])[F:7])[CH3:2].[H-].[Na+].[Br:15][C:16]1[N:21]=[C:20]([C:22]2([CH3:37])[CH2:24][N:23]2[S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[N+:34]([O-:36])=[O:35])(=[O:27])=[O:26])[C:19]([F:38])=[CH:18][CH:17]=1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:12])[C@:5]([O:11][CH2:37][C:22]([C:20]1[C:19]([F:38])=[CH:18][CH:17]=[C:16]([Br:15])[N:21]=1)([NH:23][S:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N+:34]([O-:36])=[O:35])(=[O:26])=[O:27])[CH3:24])([CH3:10])[C:6]([F:7])([F:8])[F:9])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 26985621(R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl esterHCID 866680366-Bromo-3-fluoro-2-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine

Product 1

HCID 86668035(R)-2-[2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]3,3,3-trifluoro-2-methyl-propionic acid ethyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl ester (715 mg, 3.84 mmol) in DMF (4 ml) was added NaH (55%) (154 mg, 3.84 mmol) at room temperature and the reaction mixture was stirred for 30 minutes at room temperature. A solution of 6-bromo-3-fluoro-2-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine (800 mg, 1.922 mmol) in DMF (9 ml) was added and the reaction mixture was stirred at room temperature for 48 hours. The reaction mixture was poured onto a mixture of ice/2N HCl/t-butyl-methylether. The organic layer was washed with sat. sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and evaporated. Silica gel chromatography (cyclohexane/ethyl acetate) afforded the title compound as a mixture of 2 diastereoisomers. 300 mg (26% yield). TLC (cyclohexane/ethyl acetate 2:1) Rf=0.42; LCMS RtH5=1.25 min (100%, TIC ES+ 602, 604).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 48 hours
  2. washThe organic layer was washed with sat. sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-86d7c64880614d8ba5617b2453448fae
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

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