Sodium hydride → HCID 57937566, compound

HRID 1435134Notes

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+].[Cl:17][C:18]1[CH:23]=[C:22](F)[CH:21]=[CH:20][N:19]=1>C1COCC1>[Cl:17][C:18]1[CH:23]=[C:22]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:21]=[CH:20][N:19]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1,1-Dimethylethyl 4-hydroxy-1-piperidinecarboxylate (5.50 g, 27.4 mmol) was dissolved in 100.0 mL of THF and cooled to 0° C. Next, sodium hydride (1.19 g, 29.7 mmol, 60% dispersed in mineral oil) was added portion wise and the mixture stirred at rt for 1 h. The mixture was cooled to 0° C. again and 2-chloro-4-fluoropyridine (3.00 g, 22.8 mmol) was added dropwise as a THF solution. The reaction was allowed to stir at rt, and after 6 h TLC indicated that all of the 2-chloro-4-fluoropyridine had reacted. The mixture was again cooled to 0° C. and quenched with water. EtOAc was added and the organics separated. The organics were washed with brine and dried over anhydrous MgSO4, The crude was purified via silica gel chromatography to give 6.14 g (86% yield) of a colorless oil. 1H NMR (400 MHz, DMSO-d6) δ 8.16 (d, J=5.9 Hz, 1H), 7.12 (d, J=2.2 Hz, 1H), 6.99 (d, J=5.9 Hz, 1H), 4.62-4.87 (m, 1H), 3.51-3.69 (m, 2H), 2.96-3.22 (m, 2H), 1.78-1.93 (m, 2H), 1.41-1.57 (m, 2H), 1.36 (s, 9H).

Workup

temperatureThe mixture was cooled to 0° C. again
stirringto stir at rt
waitafter 6 h TLC indicated
temperatureThe mixture was again cooled to 0° C.
customquenched with water
additionEtOAc was added
washThe organics were washed with brine
dry with materialdried over anhydrous MgSO4
customThe crude was purified via silica gel chromatography

Sources & evidence

ORD record: ord-1333c682f5154cfaacd020fb5cfdac30
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615643B2

Reaction notes

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