Sodium hydride → HCID 68508421, compound

HRID 1715319Notes

Reaction equation

HRID 1715319 reaction equation
[CH:1]([NH:5][C:6]([CH:8]([O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([C:27]([F:30])([F:29])[F:28])[CH:20]=1)[C:9]([CH3:17])([CH3:16])[CH2:10]OS(C)(=O)=O)=[O:7])([CH2:3][CH3:4])[CH3:2].[H-].[Na+].[Cl-].[NH4+]>O1CCCC1>[C@@H:1]([N:5]1[CH2:17][C:9]([CH3:16])([CH3:10])[C@@H:8]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([C:27]([F:29])([F:30])[F:28])[CH:20]=2)[C:6]1=[O:7])([CH2:3][CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 86608971HCID 86608971, compound

Product 1

HCID 68508421HCID 68508421, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution comprised of a mixture of methanesulfonic acid 3-sec-butylcarbamoyl-3-(4-cyano-3-trifluoromethyl-phenoxy)-2,2-dimethyl-propyl ester diastereomers (1.89 g; 4.2 mmol) in tetrahydrofuran (10 mL) at ambient temperature under a nitrogen atmosphere is added a 60% sodium hydride mineral oil dispersion (0.34 g; 8.4 mmol) in portions. The reaction mixture is stirred overnight. The reaction mixture is carefully neutralized with saturated aqueous ammonium chloride and is extracted with ethyl acetate. The organic phase is washed with a brine solution and is dried over anhydrous magnesium sulfate. The organic solution is concentrated in vacuo to afford 1.47 g of a viscous residue comprised of two diastereomers; HPLC UV purity: 92% (two diastereomers.) The diastereomers are separated by flash silica column chromatography (Biotage Horizon chromatography system; 100 g of silica gel, Biotage 40+M silica cartridge.) Elution with a gradient (100% hexanes to 30% ethyl acetate over 3204 mL) will afford complete separation of the diastereomers: (3R,S)-(+)-4-(1-sec-Butyl-4,4-dimethyl-2-oxo-pyrrolidin-3-yloxy)-2-trifluoromethyl-benzonitrile. 0.365 g;; [α]58924° C.=+238° (in dichloromethane);microanalysis for C18H21F3N2O2: % C(calc/found) 61.01/60.81, % H 5.97/6.06, % N 7.91/7.66, % F 16.08/16.25.

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe organic phase is washed with a brine solution
  3. dry with materialis dried over anhydrous magnesium sulfate
  4. concentrationThe organic solution is concentrated in vacuo

Sources & evidence

ORD record
ord-44c15610540847818ec13bf4cf5eeb68
Source dataset
uspto-grants-2010_09
Patent number
US07799823B2

Reaction notes

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