Iodine → HCID 59201712, compound

HRID 451702Notes

Reaction equation

II.Br[C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([F:11])[CH:5]=1.CON(C)[C:15]([C@@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16]>C1COCC1>[F:11][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([CH3:10])[CH:7]=1)[C:15]([C@@H:17]1[CH2:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16]

Participants

Conditions

Temperature: -78 °C

Procedure

A 100 mL three-neck flask was charged with Mg (638 mg, 26.6 mmol), a small crystal of iodine. The flask was degassed and refilled into N2. A solution of 1-bromo-3-fluoro-5-methyl-benzene (5 g, 26.6 mmol) in anhydrous THF was added. The reaction mixture was stirred and heated to reflux for 2 h. Once most of the Mg disappeared the reaction was cooled to −78° C. Then (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate (1.45 g, 5.32 mmol) in anhydrous THF was added dropwise slowly, and the mixture was stirred overnight. The mixture was quenched with saturated NH4Cl solution (30 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product (R)-tert-butyl 3-(3-fluoro-5-methylbenzoyl)piperidine-1-carboxylate (1.7 g, 99%), which was used immediately without further purification.

Workup

customThe flask was degassed
additionrefilled into N2
temperatureheated
temperatureto reflux for 2 h
stirringthe mixture was stirred overnight
customThe mixture was quenched with saturated NH4Cl solution (30 mL)
extractionextracted with ethyl acetate (3×20 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-9148bed1b3194669bc4a62dadacf9b2e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08487108B2

Reaction notes

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