Diisopropylethylamine → HCID 71212160, compound

HRID 1752241Notes

Reaction equation

[O:1]=[C:2]1[C@@H:6](OS(C)(=O)=O)[CH2:5][CH2:4][NH:3]1.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[O:21])=[CH:16][C:15]=1[CH3:28].CCN(C(C)C)C(C)C>C(#N)C>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH:22]2[CH2:27][CH2:26][N:25]([C@@H:6]3[CH2:5][CH2:4][NH:3][C:2]3=[O:1])[CH2:24][CH2:23]2)=[O:21])=[CH:16][C:15]=1[CH3:28]

Participants

Conditions

Temperature: 85 °C

Procedure

In a 1 L round bottom flask was added methanesulfonic acid (S)-2-oxo-pyrrolidin-3-yl ester (prepared according to procedure in Eur. Pat. Appl., 257602, 2 Mar. 1988) (18.75 mmol, 3.36 g) and (4-methoxy-3-methyl-phenyl)-piperidin-4-yl-methanone (18.75 mmol, 4.37 g) in DIEA (75 mmol, 13.1 mL) and acetonitrile (100 mL). The reaction mixture was heated at 85° C. for 4 hours. The reaction was evaporated under a vacuum and silica gel flash column chromatography was performed on the remaining residue eluting with ethyl acetate to 20% MeOH/ethyl acetate to provide the title compound as a white solid (4 g, 67.4% yield). Calculated for C18H24N2O3 MS=316.4036. found MS (ESI) m/e 317.1863 (M+H+); 1H NMR (400 MHz, MeOD) δ ppm 1.69-1.89 (m, 4H) 2.08-2.21 (m, 1H) 2.24-2.30 (m, 1H) 2.44-2.56 (m, 1H) 2.73-2.84 (m, 1H) 2.84-2.92 (m, 1H) 3.08-3.17 (m, 1H) 3.30-3.42 (m, 6H) 3.45-3.54 (m, 1H) 3.90 (s, 3H) 6.95-7.04 (m, 1H) 7.72-7.81 (m, 1H) 7.83-7.90 (m, 1H); analytical RP-HPLC retention time=4.67 min.

Workup

customThe reaction was evaporated under a vacuum and silica gel flash column chromatography
washeluting with ethyl acetate to 20% MeOH/ethyl acetate

Sources & evidence

ORD record: ord-bec5b2a7d7ea4cfe8507460a22d3f954
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163003B2

Reaction notes

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