Triethylamine → 3-(4-(4-(Benzyloxy)phenyl)-3,3-difluoropiperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one

HRID 1507248Notes

Reaction equation

HRID 1507248 reaction equation
Br[CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([F:15])[CH:9]=2)[C:3]1=[O:16].[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][C:32]2([F:38])[F:37])=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N(CC)CC)C>O>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]2[CH2:36][CH2:35][N:34]([CH:2]3[CH2:6][CH2:5][N:4]([CH2:7][C:8]4[CH:13]=[CH:12][C:11]([CH3:14])=[C:10]([F:15])[CH:9]=4)[C:3]3=[O:16])[CH2:33][C:32]2([F:38])[F:37])=[CH:27][CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 118207299Racemic 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidineHCID 1182075963-Bromo-1-(3-fluoro-4-methyl-benzyl)pyrrolidin-2-one2×

Product 1

HCID 1182074833-(4-(4-(Benzyloxy)phenyl)-3,3-difluoropiperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 3-bromo-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (0.51 g, 1.8 mmol, Intermediate 6) and 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidine (0.3 g, 1 mmol, from step C) was added triethylamine (0.69 mL, 4.9 mmol) and the resulting mixture was heated in a sealed tube at 120° C. for 1 h. The reaction mixture was allowed to cool and then diluted with water and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over Na2SO4, filtered, and concentrated. The residue (0.45 grams, 64%, mixture of 4 diastereoisomers) was used directly in the next step without further purification, LCMS (method P) RT 1.19 min, m/z 509 (M+H+).

Workup

  1. temperatureto cool
  2. extractionthe mixture was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionThe residue (0.45 grams, 64%, mixture of 4 diastereoisomers)
  9. customwas used directly in the next step without further purification, LCMS (method P) RT 1.19 min, m/z 509 (M+H+)

Sources & evidence

ORD record
ord-049e04e4f8534fc9bd05dcfa8c520e2b
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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