1-Bromo-3-fluorobenzene → HCID 57893679, compound

HRID 1821991Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([OH:14])[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](F)[CH:20]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([O:14][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Br:18])[CH:20]=2)[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 65 °C

Procedure

Combine 4-hydroxy-cis-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 2 (preparation 3, 0.986 g) in DMF (10 mL) and add to a suspension of sodium hydride (95%, 0.127 g) in DMF (10 mL) and heat in an oil bath at 65° C. After 30 min., add 1-bromo-3-fluoro-benzene (0.96 g) and heat at 65° C. After 18 hr., partition between ethyl acetate-hexane (1:4) and saturated aqueous NaCl, dry over anhydrous sodium sulfate, evaporate and purify on a 35 g silica gel column eluting with ethyl acetate-hexane (1:9) to give the title compound as a colorless oil (0.759 g). 1H NMR (CDCl3): 7.13 (dd, 1H), 7.05 (ddd, 1H), 7.04 (m, 1H), 6.81 (ddd, 1H), 4.63 (m, 1H), 4.35 (m, 1H), 3.88 (m, 1H), 3.23 (m, 1H), 1.90 (m, 3H), 1.73 (m, 1H), 1.46 (s, 9H), 1.27 (d, J=7.0 Hz, 3H).

Workup

temperatureheat at 65° C
waitAfter 18 hr
custom, partition between ethyl acetate-hexane (1:4) and saturated aqueous NaCl
dry with materialdry over anhydrous sodium sulfate
customevaporate
custompurify on a 35 g silica gel column
washeluting with ethyl acetate-hexane (1:9)

Sources & evidence

ORD record: ord-cfb407e43fdb47789108df90d455f4ad
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07608629B2

Reaction notes

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