N-methyl-2-pyrrolidone → 4-[3-(Hydroxymethyl)-8-methylquinolin-2-yl]piperazin-2-one

HRID 1627509Notes

Reaction equation

HRID 1627509 reaction equation
Cl[C:2]1[C:11]([CH2:12][OH:13])=[CH:10][C:9]2[C:4](=[C:5]([CH3:14])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[O:15]=[C:16]1[CH2:21][NH:20][CH2:19][CH2:18][NH:17]1.CCN(C(C)C)C(C)C.CN1C(=O)CCC1>CCOC(C)=O.CCOCC>[OH:13][CH2:12][C:11]1[C:2]([N:20]2[CH2:19][CH2:18][NH:17][C:16](=[O:15])[CH2:21]2)=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[CH3:14]

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 231360Piperazin-2-oneHCID 865104(2-Chloro-8-methylquinolin-3-yl)methanol

Product 1

HCID 667764484-[3-(Hydroxymethyl)-8-methylquinolin-2-yl]piperazin-2-oneYield 51%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

(2-Chloro-8-methylquinolin-3-yl)methanol (250 mg, 1.13 mmol), 2-oxopiperazine (566 mg, 5.66 mmol), DIPEA (1 mL, 5.66 mmol) and NMP (3 mL) were combined in a sealed tube and heated to 140° C. for 24 h. After cooling, the reaction mixture was dissolved in a 1:1 mixture of EtOAc and Et2O (100 mL) and washed with saturated brine (3×25 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Purification by column chromatography on silica, eluting with 5% MeOH in DCM, afforded the title compound (155 mg, 51%) as a white solid. LCMS (ES+) 272 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. washwashed with saturated brine (3×25 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography on silica
  6. washeluting with 5% MeOH in DCM

Sources & evidence

ORD record
ord-7a3ed99e5cb44efab7d5bd516c3f8fd8
Source dataset
uspto-grants-2014_07
Patent number
US08785628B2

Reaction notes

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