Cesium carbonate → HCID 86650669, compound

HRID 1969469Notes

Reaction equation

HRID 1969469 reaction equation
[CH3:1][C:2]([NH:14][C@@H:15]1[CH2:19][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[N:17]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=2)[C:16]1=[O:37])([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[N:5]=1)[CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:45][CH2:46][CH2:47][F:48]>CN(C=O)C.CCOC(C)=O>[CH3:3][C:2]([NH:14][C@@H:15]1[CH2:19][C@H:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:45][CH2:46][CH2:47][F:48])[CH:21]=2)[N:17]([C:27]2[CH:28]=[CH:29][C:30]([C:33]([F:35])([F:34])[F:36])=[CH:31][CH:32]=2)[C:16]1=[O:37])([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[N:5]=1)[CH3:1]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 67699Propane, 1-bromo-3-fluoro-HCID 86650659HCID 86650659, compound

Product 1

HCID 86650669HCID 86650669, compoundYield 77.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve (3R,5R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-5-(3-hydroxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (520 mg, 0.99 mmol) in DMF (9 mL) and add cesium carbonate (1.9 g, 5.9 mmol) and 1-bromo-3-fluoro-propane (170 mg, 1.19 mmol). Stir the mixture at ambient temperature for 19.5 hours and dilute with EtOAc. Wash with brine, dry over sodium sulfate, filter, and concentrate the organic to residue. Purify the residue by silica gel chromatography (30% EtOAc-hexane) to obtain (3R,5R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-5-[3-(3-fluoro-propoxy)-phenyl]-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (447 mg, 77%) as a colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 8.08 (d, J=7.9 Hz, 1H), 8.01 (dd, J=7.7, 7.7 Hz, 1H), 7.70 (d, J=7.5 Hz, 1H), 7.58 (d, J=8.8 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.13 (dd, J=7.9, 7.9 Hz, 1H), 6.82-6.70 (m, 3H), 5.18 (dd, J=9.7, 6.6 Hz, 1H), 4.58 (t, J=5.9 Hz, 1H), 4.46 (t, J=5.9 Hz, 1H), 4.02-3.88 (m, 2H), 3.47-3.39 (m, 1H), 2.96 (d, J=3.5 Hz, 1H), 2.73-2.63 (m, 1H), 2.06-1.92 (m, 2H), 1.63 (dd, J=22.0, 10.5 Hz, 1H), 1.47 (s, 3H), 1.42 (s, 3H). LC-MS ESI m/z: 584.0 (M+H)+, Tr=3.61 min., method 1.

Workup

  1. washWash with brine
  2. dry with materialdry over sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate the organic to residue
  5. customPurify the residue by silica gel chromatography (30% EtOAc-hexane)

Sources & evidence

ORD record
ord-97096cd694b94fff8e7c25f0c08a3f18
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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