Sodium hydride → HCID 68710819, compound

HRID 2239345Notes

Reaction equation

[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].F[C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[C:21]#[N:22]>CN(C=O)C>[C:21]([C:20]1[CH:19]=[C:18]([CH:25]=[CH:24][CH:23]=1)[O:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)#[N:22]

Participants

Conditions

Temperature: 0 °C

Procedure

tert-Butyl 4-hydroxypiperidine-1-carboxylate (3.49 g, 17.3 mmol) was dissolved in DMF (35 ml) and cooled to 0° C. NaH (1.19 g, 24.8 mmol) was added in small portions over 20 minutes. The reaction was stirred for 30 minutes at 0° C. and 3-fluorobenzonitrile (3.1 ml, 29.0 mmol) added. The reaction was allowed to warm to r.t. over 1 h, stirred for a further 16 h and then quenched by addition of water. The reaction mixture was separated between water (500 ml) and DCM (2×500 ml). The combined organics were washed with water (500 ml), dried through a phase separator and evaporated in vacuo. Purification by flash silica gel chromatography using a 100 g Biotage column with a gradient of 5-40% EtOAc in heptane yielded the title compound as a white solid. Yield: 4.2 g (81%). 1H NMR (400 MHz, CDCl3) δ 7.34 (t, 1H, J=7.9 Hz), 7.21 (d, 1H, J=7.7), 7.14-7.08 (m, 2H), 4.46 (m, 1H), 3.67 (m, 2H), 3.33 (m, 2H), 1.90 (m, 2H), 1.72 (m, 2H), 1.45 (s, 9H).

Workup

temperatureto warm to r.t. over 1 h
stirringstirred for a further 16 h
customquenched by addition of water
customThe reaction mixture was separated between water (500 ml) and DCM (2×500 ml)
washThe combined organics were washed with water (500 ml)
customdried through a phase separator
customevaporated in vacuo
customPurification by flash silica gel chromatography

Sources & evidence

ORD record: ord-084ea4f0d1824889915979232c3b8c3e
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723331B2

Reaction notes

Loading…