4-Methylmorpholine → HCID 67444559, compound

HRID 1667254Notes

Reaction equation

HRID 1667254 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[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:31][C:32]([F:41])([F:40])[C:33]1[CH:34]=[CH:35][C:36]([NH2:39])=[N:37][CH:38]=1.CN1CCOCC1>ClCCl.CN(C)C=O>[F:24][C:21]1[CH:20]=[CH:19][C:18]([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14]([NH:39][C:36]3[CH:35]=[CH:34][C:33]([C:32]([F:40])([F:31])[F:41])=[CH:38][N:37]=3)=[O:16])[C:9]2=[O:17])=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 7358622-Amino-5-(trifluoromethyl)pyridineHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 67444559HCID 67444559, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.158 g, 0.477 mmol; Example 58D) in dichloromethane (2 mL) was added a catalytic amount of N,N-dimethylformamide followed by oxalyl dichloride (2.0 Min dichloromethane) (0.358 mL, 0.715 mmol). After stirring for 30 minutes, the reaction was concentrated. The residue was dissolved in dichloromethane (2 mL) and 5-(trifluoromethyl)pyridin-2-amine (0.066 g, 0.405 mmol) and N-methylmorpholine (0.079 mL, 0.715 mmol) were added. After stirring for 2 hours, 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 75% ethyl acetate/hexanes (Flow=30 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.55 (d, J=12.2, 1H), 8.25 (d, J=8.8, 1H), 7.92 (dd, J=2.2, 8.8, 1H), 7.33 (ddd, J=2.7, 5.3, 7.1, 4H), 7.06-6.96 (m, 4H), 4.22 (s, 2H), 3.55 (t, J=6.5, 2H), 2.83 (t, J=6.5, 2H); MS (ESI+) m/z 467.1 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionThe residue was dissolved in dichloromethane (2 mL)
  3. stirringAfter stirring for 2 hours
  4. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes (Flow=30 mL/minute) over 30 minutes

Sources & evidence

ORD record
ord-70214cd91b5048879117f9a8f417edb0
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

Loading…