Methanol → HCID 68465097, compound

HRID 218061Notes

Reaction equation

HRID 218061 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][CH:12]([C:16](=[O:19])[CH2:17]Br)[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][OH:21]>FC(F)(F)S([O-])(=O)=O.[Ag+].C(=O)([O-])[O-].[Ag+2]>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][CH:12]([C:16](=[O:19])[CH2:17][O:21][CH3:20])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 887MethanolHCID 86643296HCID 86643296, compound

Product 1

HCID 68465097HCID 68465097, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 178418647HCID 178418647, compoundCatalyst

Procedure

A mixture of 1-(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-7-yl)-2-bromo-1-ethanone (0.126 g, 0.360 mmol), silver trifluoromethanesulfonate (0.10 g, 0.39 mmol), and silver carbonate (0.10 g, 0.36 mmol) in methanol (4.0 mL) was stirred in the dark for 2 days at ambient temperature. The reaction was filtered, and the filtrate was concentrated and purified by silica gel column chromatography, eluting with 30-40% ethyl acetate in hexanes, to obtain 0.062 g (61% yield) of 1-(3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-7-yl)-2-methoxy-1-ethanone as an oil. This was dissolved in dichloromethane (2.0 mL), treated with TFA (0.5 mL), and was stirred at ambient temperature for 2 h. The volatiles were evaporated, and the residue was vacuum dried to obtain 0.045 g of 1-(3-azabicyclo[3.3.0]oct-7-yl)-2-methoxy-1-ethanone trifluoroacetate, as an off-white solid (mixture of cis and trans isomers) (1H NMR (CD3OD, 300 MHz): δ 4.17 (s, 2H), 3.39 (s, 3H), 3.36-3.30 (m, 2H), 3.19-3.12 (m, 3H), 3.00-2.91 (m, 2H), 2.30-2.20 (m, 2H), 1.64-1.75 (m, 2H); MS (m/z): 184 (M+1)). This material exhibited Ki values at rat and human α4β2 of 32 nM and 31 nM respectively and did not pass HIS for α7.

Workup

  1. filtrationThe reaction was filtered
  2. concentrationthe filtrate was concentrated
  3. custompurified by silica gel column chromatography
  4. washeluting with 30-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-33a2534f04e84c4c9e954f627056f151
Source dataset
uspto-grants-2012_06
Patent number
US08198296B2

Reaction notes

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