4-Methylmorpholine → 2-[3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]acetamide

HRID 1667266Notes

Reaction equation

HRID 1667266 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[F:24][C:25]([F:34])([F:33])[C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1.CN1CCOCC1>ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([NH:32][C:29]3[CH:28]=[CH:27][C:26]([C:25]([F:33])([F:24])[F:34])=[CH:31][N:30]=3)=[O:16])[C:9]2=[O:17])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 673576422-(3-(4-Fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 673610562-[3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[5-(trifluoromethyl)pyridin-2-yl]acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(3-(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.088 g, 0.370 mmol; Example 216A) in dichloromethane (1 mL) was added oxalyl dichloride (0.308 mL, 0.617 mmol). After 30 minutes, the reaction was concentrated and dried. This residue was dissolved in dichloromethane (1 mL) and 5-(trifluoromethyl)pyridin-2-amine (0.050 g, 0.308 mmol) was added followed by 4-methylmorpholine (0.068 mL, 0.617 mmol). After stirring for 30 minutes, the reaction was loaded onto a GraceResolv™ 12 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.67 (s, 1H), 8.57-8.52 (m, 1H), 8.28 (d, J=8.7, 1H), 7.92 (dd, J=2.3, 8.8, 1H), 7.35-7.21 (m, 2H), 7.09-6.99 (m, 2H), 4.25 (d, J=16.0, 1H), 4.18 (d, J=16.0, 1H), 3.78 (t, J=9.0, 1H), 3.69-3.59 (m, 2H), 2.63 (m, 1H), 2.23 (m, 1H); MS (ESI+) m/z 382.0 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. customdried
  3. dissolutionThis residue was dissolved in dichloromethane (1 mL)
  4. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes (Flow=20 mL/minute) over 30 minutes

Sources & evidence

ORD record
ord-1ecd5fc6f84c48709e9cdd7524f85bfa
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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