1,3-Dibromo-5-fluorobenzene → HCID 69351008, compound

HRID 970725Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([Br:9])[CH:3]=1.[Li]CCCC.[CH3:15][N:16]([CH3:24])[CH:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1>C(OCC)C>[Br:9][C:4]1[CH:3]=[C:2]([C:20]2([OH:23])[CH2:21][CH2:22][CH:17]([N:16]([CH3:24])[CH3:15])[CH2:18][CH2:19]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

Conditions

Temperature: -60 °C

Procedure

Dissolve 1,3-dibromo-5-fluoro-benzene (19.8 g, 77.90 mmol) in dry diethyl ether (300 mL) and cool to −60° C. Add 1.6M n-BuLi in hexanes (50.9 mL, 81.44 mmol) dropwise over 15 min. and stir an additional 15 min. Add a pre-cooled (−60° C.) solution of 4-dimethylamino-cyclohexanone (10.0 g, 70.8 mmol) in diethyl ether (200 mL) dropwise over 30 min. Stir at −60° C. to −20° C. for 2 hr., then warm to ambient temperature and stir for 1 hr. Quench the reaction with water (200 mL) and extract with ethyl acetate (3×200 mL). Dry over sodium sulfate, filter and concentrate. Purify the residue by flash chromatography (15% 2M NH3/MeOH in DCM) to obtain 1-(3-Bromo-5-fluoro-phenyl)-4-dimethylamino-cyclohexanol as a white foam (14.5 g, 64.8%). MS (ES) m/z=316 (M−H)−, 318 (M+H)+; 1H NMR (CDCl3): δ 7.41 (d, 1H, J=2 Hz), 7.15 (m, 2H), 2.3 (m, 8H), 1.78 (m, 8H).

Workup

additionAdd
stirringStir at −60° C. to −20° C. for 2 hr
temperature, then warm to ambient temperature
stirringstir for 1 hr
customQuench
customthe reaction with water (200 mL)
extractionextract with ethyl acetate (3×200 mL)
dry with materialDry over sodium sulfate
filtrationfilter
concentrationconcentrate
customPurify the residue by flash chromatography (15% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-95fe0717ff6044059ecb0767d2fea42e
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07312236B2

Reaction notes

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