Sodium hydride → HCID 178472477, compound

HRID 1675336Notes

Reaction equation

[OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.[F:13][C:14]1[CH:19]=[C:18](F)[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22].[H-].[Na+]>CN(C=O)C>[F:13][C:14]1[CH:19]=[C:18]([CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22])[O:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]1

Participants

Conditions

Temperature: 5 °C

Procedure

To a stirred solution of ethyl 4-hydroxycyclohexanecarboxylate (20.7 g, 120.19 mmol) and 2,4-difluoronitrobenzene (19.125 g, 120.19 mmol) in DMF at 5° C. was added NaH (5.05 g, 126.2 mmol) in one portion, resulting in a slow exotherm to 10° C. The reaction was stirred at 5° C. for 1 hour then allowed to warm to ambient temperature and stirred for 24 hr. The reaction was cooled to 0° C. and quenched with water (˜400 mL). The mixture was extracted with EtOAc (3×˜150 mL), the organic layers combined, washed with brine (2×˜100 mL), dried (MgSO4), filtered and evaporated to an orange oil (36 g). The crude residue was purified by preparative HPLC (silica, 4:1 ethyl acetate:isohexane) to give the title compound (4.5 g, 12%) as a pale orange oil.

Workup

customresulting in a slow exotherm to 10° C
temperatureto warm to ambient temperature
stirringstirred for 24 hr
temperatureThe reaction was cooled to 0° C.
customquenched with water (˜400 mL)
extractionThe mixture was extracted with EtOAc (3×˜150 mL)
washwashed with brine (2×˜100 mL)
dry with materialdried (MgSO4)
filtrationfiltered
customevaporated to an orange oil (36 g)
customThe crude residue was purified by preparative HPLC (silica, 4:1 ethyl acetate:isohexane)

Sources & evidence

ORD record: ord-79e37e80ea3040438b0fcde74d0cf0b3
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003676B2

Reaction notes

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