Sodium hydride → HCID 59737058, compound

HRID 1660722Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH2:10]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26]I)[CH2:21]1)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C=O)C>[CH2:10]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([CH2:26][N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]2=[O:1])[CH2:21]1)=[O:19])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of 2-hydroxypyridine (200 mg, 2 mmol) in DMF (5 mL) was added NaH (60% mixture in mineral oil, 100 mg, 2.5 mmol). The mixture was stirred at 80° C. under N2 for 2 h, and then 3-iodomethylpiperidine-1-carboxylic acid benzyl ester (720 mg, 2 mmol) was added. The mixture was stirred at 80° C. for 10 h, cooled to room temperature, quenched with water, and extracted with EtOAc. The combined organic layers were washed with brine, dried, and concentrated. The residue was purified by chromatography with CH2Cl2-EtOAc-MeOH (10:10:1) to give a viscous oil (475 mg, 73%). 1H NMR (CDCl3) δ 7.30 (m, 7H), 6.55 (d, 1H, J=9.0 Hz), 6.12 (m, 1H), 5.11 (s, 2H), 4.10-3.50 (m, 4H), 3.09 (t, 1H, J=10.2 Hz), 2.92 (dd, 1H, J=13.2, 9.0 Hz), 2.10 (m, 1H), 1.85-1.20 (m, 4H).

Workup

stirringThe mixture was stirred at 80° C. for 10 h
temperaturecooled to room temperature
customquenched with water
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
customdried
concentrationconcentrated
customThe residue was purified by chromatography with CH2Cl2-EtOAc-MeOH (10:10:1)

Sources & evidence

ORD record: ord-b3ec403fc54d48738cd1f935d676b5f0
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030300B2

Reaction notes

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