Sodium hydride → HCID 86648405, compound

HRID 409477Notes

Reaction equation

HRID 409477 reaction equation
C([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C:14]2[N:19]=[CH:18][C:17]([Br:20])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH2:21][CH3:22])=[O:7])(C)(C)C.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:28]Br.[H-].[Na+]>CN(C=O)C>[F:23][C:24]([F:37])([F:38])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:32]=1)[CH2:28][N:13]([C:14]1[N:15]=[CH:16][C:17]([Br:20])=[CH:18][N:19]=1)[C@@H:11]1[CH2:12][N:8]([C:6]([OH:5])=[O:7])[C@H:9]([CH2:21][CH3:22])[CH2:10]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 59614361HCID 59614361, compound

Product 1

HCID 86648405HCID 86648405, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (2R,4S)-4-(5-bromo-pyrimidin-2-ylamino)-2-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (13.0 mmol; 4.84 g), 3,5-bis(trifluoromethyl)benzyl bromide (26.0 mmol; 7.98 g) and sodium hydride (60% dispersion in mineral oil, 39.0 mmol; 1.56 g) in DMF (52 mL) is stirred for 1.5 hours at room temperature under nitrogen. The reaction mixture is quenched with water then saturated ammonium chloride solution. The product is extracted twice with EtOAc. The combined organic layer is washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc) to give (2R,4S)-4-[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-2-ethyl-pyrrolidine-1-carboxylic acid tent-butyl ester (5.57 g, 72%).

Workup

  1. customThe reaction mixture is quenched with water
  2. extractionThe product is extracted twice with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue is purified by silica gel column chromatography (eluent: n-hexane/EtOAc)

Sources & evidence

ORD record
ord-fc313d6ed9fb4c0c8f3812b532b03b85
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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