Ammonium Hydroxide → HCID 86650659, compound

HRID 1969448Notes

Reaction equation

HRID 1969448 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]([O:26]C)[CH:21]=2)[N:17]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[C:16]1=[O:38])([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([F:13])([F:12])[F:11])[N:5]=1)[CH3:3].Cl.N1C=CC=CC=1.[OH-].[NH4+]>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]([OH:26])[CH:21]=2)[N:17]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:35])([F:37])[F:36])=[CH:32][CH:33]=2)[C:16]1=[O:38])([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

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 10176127Pyridinium chlorideHCID 86650657HCID 86650657, compound

Product 1

HCID 86650659HCID 86650659, compoundYield 32.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
185 °C

Procedure

Add (3R,5R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-5-(3-methoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (1.9 g, 3.4 mmol) to pyridine hydrochloride (28.6 g, 247.8 mmol). Plunge the mixture into a 185° C. oil bath and heat for 2 hours. Cool to ambient temperature and dilute with water (175 mL). Make the pH basic by ammonium hydroxide addition and extract with EtOAc. Wash with brine, dry over sodium sulfate, filter and concentrate the organic to residue. Purify the residue by silica gel chromatography (20%-30% EtOAc-hexane) to obtain (3R,5R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-5-(3-hydroxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one (0.58 g, 32%) as a white foam. LC-MS ESI m/z: 524.2 (M+H)+, Tr=2.91 min., method 1.

Workup

  1. temperatureCool to ambient temperature
  2. extractionextract with EtOAc
  3. washWash with brine
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate the organic to residue
  7. customPurify the residue by silica gel chromatography (20%-30% EtOAc-hexane)

Sources & evidence

ORD record
ord-06296cd7a6a549169b67556679e63c9e
Source dataset
uspto-grants-2013_04
Patent number
US08426448B2

Reaction notes

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