Sodium Hydroxide → 3-(3,4-Dichlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol

HRID 987581Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([Cl:9])[CH:3]=1.[Li]CCCC.[CH3:15][N:16]1[CH:20]2[CH2:21][C:22]([CH2:24][CH:17]1[CH2:18][CH2:19]2)=[O:23].[OH-].[Na+]>C1COCC1>[Cl:9][C:4]1[CH:3]=[C:2]([C:22]2([OH:23])[CH2:21][CH:20]3[N:16]([CH3:15])[CH:17]([CH2:18][CH2:19]3)[CH2:24]2)[CH:7]=[CH:6][C:5]=1[Cl:8]

Participants

Conditions

Temperature: -78 °C

Procedure

To 4.0 mL (7.04 g, 31.18 mmol) 4-bromo-1,2-dichloro-benzene in 100 mL THF at −78° C. is added 12.47 mL of a 2.5 M solution of n-BuLi in hexanes in drops over 5 min. After stirring at −78° C. for 45 min, 4.34 g (31.18 mmol) tropinone is added as a solid. The resulting mixture is warmed to 23° C. and stirred for 18 h. After pouring into 2.5 N NaOH, the reaction mixture is extracted with 2×100 mL EtOAc, the organics are combined and washed with 1×100 mL H2O, 1×100 mL brine, dried over MgSO4, filtered and evaporated to an off-white solid. Flash chromatography on SiO2 gel, eluting with CHCl3/MeOH (20/1 to 5/1), gives 2.58 g (9.02 mmol, a 28% yield) of the title compound as a white solid. mp: 153-154° C.; MS (ES) m/z 287 (MH)+.

Workup

temperatureThe resulting mixture is warmed to 23° C.
stirringstirred for 18 h
extractionthe reaction mixture is extracted with 2×100 mL EtOAc
washwashed with 1×100 mL H2O, 1×100 mL brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated to an off-white solid
washFlash chromatography on SiO2 gel, eluting with CHCl3/MeOH (20/1 to 5/1)
customgives 2.58 g (9.02 mmol

Sources & evidence

ORD record: ord-841e0015776b4437b5b8335f2ecc3e15
Source dataset: uspto-grants-2003_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06632824B2

Reaction notes

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