4-Methylmorpholine → 2-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]acetamide

HRID 1667261Notes

Reaction equation

HRID 1667261 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[N:38]=[CH:37][C:36]([NH2:39])=[CH:35][CH:34]=1.CN1CCOCC1>ClCCl.CN(C)C=O>[F:24][C:21]1[CH:22]=[CH:23][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:37]=[N:38][C:33]([C:32]([F:41])([F:31])[F:40])=[CH:34][CH:35]=3)=[O:16])[C:9]2=[O:17])=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 674443022-[3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl]-N-[6-(trifluoromethyl)pyridin-3-yl]acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.255 g, 0.771 mmol; Example 58D) in dichloromethane (3 mL) was added a catalytic amount of N,N-dimethylformamide followed by oxalyl dichloride (2.0 Min dichloromethane) (0.617 mL, 1.234 mmol). The reaction was stirred for 1 hour, after which a reddish solution resulted. The reaction was concentrated and dried under high vacuum. The residue was dissolved in dichloromethane (3 mL) and 6-(trifluoromethyl)pyridin-3-amine (0.100 g, 0.617 mmol) and 4-methylmorpholine (0.136 mL, 1.234 mmol) were added. After stirring for 1 hour, the reaction was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 60% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 8.51 (d, J=2.5, 1H), 8.11 (dd, J=2.3, 8.7, 1H), 7.64-7.58 (m, 1H), 7.33-7.23 (m, 4H), 7.06-6.96 (m, 4H), 4.17 (s, 2H), 3.60 (t, J=6.5, 2H), 2.83 (t, J=6.5, 2H); MS (ESI+) m/z 476.0 (M+H)+.

Workup

  1. customafter which a reddish solution resulted
  2. concentrationThe reaction was concentrated
  3. customdried under high vacuum
  4. dissolutionThe residue was dissolved in dichloromethane (3 mL)
  5. stirringAfter stirring for 1 hour
  6. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 60% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record
ord-3c8de42bbd874d40a3ddac5c2bf93de5
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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