Sodium Chloride → HCID 71522918, compound

HRID 2178540Notes

Reaction equation

HRID 2178540 reaction equation
F[C:2]1[N:7]=[C:6]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]3[C:16]([N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]4=[O:27])=[N:17][CH:18]=[CH:19][CH:20]=3)[CH2:9]2)[CH:5]=[CH:4][CH:3]=1.[F:28][C:29]([F:33])([F:32])[CH2:30][OH:31].CC([O-])(C)C.[K+].[Na+].[Cl-]>CS(C)=O.C(OCC)(=O)C>[NH4+:7].[OH-:27].[F:28][C:29]([F:33])([F:32])[CH2:30][O:31][C:2]1[N:7]=[C:6]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][C:15]3[C:16]([N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]4=[O:27])=[N:17][CH:18]=[CH:19][CH:20]=3)[CH2:9]2)[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 64092,2,2-Trifluoroethanol2×HCID 23665647Potassium tert-butoxideHCID 89500529HCID 89500529, compound

Product 2

HCID 14923Ammonium HydroxideYield 0.05%HCID 71522918HCID 71522918, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3-{2-[3-(6-fluoropyridin-2-yl)pyrrolidin-1-yl]ethyl}pyridin-2-yl)piperidin-2-one a15-1 (32 mg, 0.087 mmol, 1 eq), 2,2,2-trifluoroethanol (13 mg, 0.13 mmol, 1.5 eq) and t-BuOK (48.8 mg, 0.43 mmol, 5 eq) are dissolved in DMSO. The reaction mixture is stirred at room temperature. After 2 hours, 2,2,2-trifluoroethanol (8.7 mg, 0.087 mmol, 1 eq) is added and the reaction mixture is stirred overnight. Ethyl acetate and aqueous saturated NaCl solution are then added, the two phases separated and the aqueous layer is reextracted with ethyl acetate (3 times). The organic layers are pooled, dried with MgSO4, filtered and condensed under reduced pressure. The residue is purified by basic reverse phase chromatography (gradient: water/acetonitrile/solvent C from 90/0/10 to 5/85/10 in 10 minutes; solvent C: acetonitrile/water 1/1+NH4CO3 0.4% w/v and NH4OH 0.05% v/v) to afford 11.7 mg of 1-[3-(2-{3-[6-(2,2,2-trifluoroethoxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one 108.

Workup

  1. stirringthe reaction mixture is stirred overnight
  2. customthe two phases separated
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. customcondensed under reduced pressure
  6. customThe residue is purified by basic reverse phase chromatography (gradient
  7. waitwater/acetonitrile/solvent C from 90/0/10 to 5/85/10 in 10 minutes

Sources & evidence

ORD record
ord-140ed79932d14f4f97cbcbe46bc44f05
Source dataset
uspto-grants-2015_06
Patent number
US09067930B2

Reaction notes

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