Triethylamine → Ethyl 2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetate

HRID 1752254Notes

Reaction equation

HRID 1752254 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[O:11])=[CH:6][CH:5]=1.C(N(CC)CC)C.Br[CH:26]1[CH2:30][CH2:29][N:28]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:27]1=[O:37]>C(#N)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]([CH:12]2[CH2:17][CH2:16][N:15]([CH:26]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:27]3=[O:37])[CH2:14][CH2:13]2)=[O:11])=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27405874-(4-Methoxybenzoyl)piperidine hydrochlorideHCID 14257595Ethyl 2-(3-bromo-2-oxopyrrolidin-1-yl)acetate

Product 1

HCID 71212189Ethyl 2-(3-(4-(4-methoxybenzoyl)piperidin-1-yl)-2-oxopyrrolidin-1-yl)acetateYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
40 °C

Procedure

(4-Methoxyphenyl)(piperidin-4-yl)methanone hydrochloride (524 mg, 2.05 mmol) was stirred at room temperature with triethylamine (0.657 mL, 477 mg, 4.71 mmol) in acetonitrile (80 mL). A solution of ethyl 2-(3-bromo-2-oxopyrrolidin-1-yl)acetate (513 mg, 2.05 mmol) in acetonitrile (20 mL) was added to the mix. The reaction was stirred 3 hours at 40° C. and then overnight at 50° C. After 24 hours the reaction was not complete and the reaction was stirred an additional 48 hours at 70° C. then allowed to cool to room temperature. The solvents were removed in vacuo. The crude orange solid was eluted through a silica gel column with a 0 to 10% methanol/dichloromethane gradient to afford the title racemic compound (730 mg, 87% yield, 95% purity) as a thick amber oil. MS (ESI) [m/e, (M+H)+]=389.5. 1H NMR (400 MHz, chloroform-d) δ ppm 7.90-7.95 (m, 2H), 6.91-6.96 (m, 2H), 4.17-4.24 (m, 2H), 3.95-4.17 (m, 2H), 3.88 (s, 3H), 3.56-3.64 (m, 1H), 3.36-3.50 (m, 2H), 3.18-3.29 (m, 1H), 3.04-3.13 (m, 1H), 2.93-3.04 (m, 2H), 2.41-2.56 (m, 1H), 2.20-2.35 (m, 1H), 2.04-2.19 (m, 1H), 1.80-1.95 (m, 4H), 1.26-1.32 (m, 3H).

Workup

  1. customovernight
  2. customat 50° C
  3. waitAfter 24 hours the reaction was not
  4. stirringcomplete and the reaction was stirred an additional 48 hours at 70° C.
  5. temperatureto cool to room temperature
  6. customThe solvents were removed in vacuo
  7. washThe crude orange solid was eluted through a silica gel column with a 0 to 10% methanol/dichloromethane gradient
  8. customto afford the title racemic compound (730 mg, 87% yield, 95% purity) as a thick amber oil

Sources & evidence

ORD record
ord-fd73d6b7ec1b486b927f1e214f4ad9de
Source dataset
uspto-grants-2015_10
Patent number
US09163003B2

Reaction notes

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