2-Bromonaphthalene → 3-Hydroxy-3-naphthalen-2-yl-8-aza-bicyclo[3.2.1]octane-8-carboxylic Acid Tert-Butyl Ester

HRID 987563Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.[C:12]([O:16][C:17]([N:19]1[CH:24]2[CH2:25][CH2:26][CH:20]1[CH2:21][C:22](=[O:27])[CH2:23]2)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C1COCC1>[C:12]([O:16][C:17]([N:19]1[CH:24]2[CH2:25][CH2:26][CH:20]1[CH2:21][C:22]([OH:27])([C:2]1[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=1)[CH2:23]2)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: 23 °C

Procedure

To a −78° C. solution of 6.20 g (29.9 mmol) 2-bromonaphthalene and 125 mL THF is added 12 mL of 2.5 M n-BuLi/hexanes. After stirring at −78° C. for 30 mins a solution of 6.40 g (28.4 mmol) 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester and 14 mL THF is added dropwise. The reaction is allowed to proceed at −78° C. for 30 mins and then warmed to 23° C. over 6 h. After quenching with 100 mL 1N NaOH and extraction with 3×100 mL of EtOAc, the combined organics are washed with 1×100 mL H2O, 1×100 mL brine, dried over MgSO4, filtered, and the volatiles removed. Flash chromatography in SiO2 gel, eluting with hexanes/EtOAc (4/1 to 1/1) gives 7.00 g (19.8 mmol, a 66% yield) of the title compound as a white solid. MS (ES) m/z 354 (M++H, 100).

Workup

additionis added dropwise
customAfter quenching with 100 mL 1N NaOH and extraction with 3×100 mL of EtOAc
washthe combined organics are washed with 1×100 mL H2O, 1×100 mL brine
dry with materialdried over MgSO4
filtrationfiltered
customthe volatiles removed
washFlash chromatography in SiO2 gel, eluting with hexanes/EtOAc (4/1 to 1/1)
customgives 7.00 g (19.8 mmol

Sources & evidence

ORD record: ord-c123b345066642c190165ea381a96d4d
Source dataset: uspto-grants-2003_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06632824B2

Reaction notes

Loading…