Chloroacetonitrile → {(R)-3-[4-(4-Methoxy-3-methyl-benzoyl)-piperidin-1-yl]-2-oxo-pyrrolidin-1-yl}-acetonitrile

HRID 1752251Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][NH:17][C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23].Cl[CH2:25][C:26]#[N:27].[H-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([C@@H:15]3[CH2:19][CH2:18][N:17]([CH2:25][C:26]#[N:27])[C:16]3=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][C:4]=1[CH3:23]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (R)-3-[4-(4-methoxy-3-methyl-benzoyl)-piperidin-1-yl]-pyrrolidin-2-one (6.32 mmol, 2.0 g) and chloroacetonitrile (6.32 mmol, 0.48 g) in THF (50 mL) was added sodium hydride (60%, 9.48 mmol, 0.38 g) and heated to 70° C. for 30 min. The reaction was allowed to cool to ambient temperature and dried under vacuum. Flash column chromatography (silica) was performed eluting with ethyl acetate to 20% MeOH/ethyl acetate and provided the title compound as an off-white residue (1.1 g, 49% yield). Calculated molecular formula=C20H25N3O3=355.4406. found MS (ESI) m/e 356.1978 (M+H+); analytical RP-HPLC (Novapak 150×3.9 mm C18 column: mobile phase: 10-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 5 min.) retention time=2.591 min.

Workup

temperatureto cool to ambient temperature
customdried under vacuum
washFlash column chromatography (silica) was performed eluting with ethyl acetate to 20% MeOH/ethyl acetate

Sources & evidence

ORD record: ord-2a97ee4c97d848928a759ae899257f6b
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163003B2

Reaction notes

Loading…