Sodium hydride → (R)-2-[(RS)-2-(2-Bromo-5-fluoro-pyridin-4-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

HRID 474085Notes

Reaction equation

HRID 474085 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]2([CH3:23])[CH2:10][N:9]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[C:5]([F:24])=[CH:4][N:3]=1.[CH2:25]([O:27][C:28](=[O:36])[C@:29]([OH:35])([CH3:34])[C:30]([F:33])([F:32])[F:31])[CH3:26].[H-].[Na+]>CN(C=O)C>[CH2:25]([O:27][C:28](=[O:36])[C@:29]([O:35][CH2:10][C:8]([C:6]1[C:5]([F:24])=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=1)([NH:9][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[CH3:23])([CH3:34])[C:30]([F:31])([F:32])[F:33])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 26985621(R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl esterHCID 866680552-Bromo-5-fluoro-4-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine

Product 1

HCID 86668056(R)-2-[(RS)-2-(2-Bromo-5-fluoro-pyridin-4-yl)-2-(2-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-bromo-5-fluoro-4-[2-methyl-1-(2-nitro-benzenesulfonyl)-aziridin-2-yl]-pyridine (795 mg, 1.91 mmol) and (R)-3,3,3-trifluoro-2-hydroxy-2-methyl-propionic acid ethyl ester (498 mg, 2.67 mmol) in DMF (8 ml, soln. predried over mol. sieves) was added NaH (99 mg of a 60% dispersion in mineral oil, 2.48 mmol) and the reaction mixture was stirred at rt for 3 h. The reaction mixture was quenched with aq. 1N HCl and diluted with H2O and TBME. The phases were separated and the aq. phase was twice extracted with TBME. The combined org. phases were washed with H2O, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (heptane:EtOAc 1:1) yielded the title compound (diastereomer mixture) as a colourless solid. HPLC RtH4=1.26 min; ESIMS: 602, 604 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 7.99 (m, 1H), 7.95-7.93 (m, 1H), 7.79-7.61 (m, 4H), 6.94 (m, 1H), 4.45-4.33 (m, 2H), 3.94-3.81 (m, 2H), 1.85 (m, 3H), 1.61 (m, 3H), 1.40-1.34 (m, 3H).

Workup

  1. customThe reaction mixture was quenched with aq. 1N HCl
  2. additiondiluted with H2O and TBME
  3. customThe phases were separated
  4. extractionthe aq. phase was twice extracted with TBME
  5. washphases were washed with H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c0a430863e274e34ae7925b6c6600d47
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

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