Hydrochloric Acid → methyl 2-fluoro-4-((1S,4S)-5-(3-(trifluoromethyl)phenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)benzoate

HRID 718070Notes

Reaction equation

HRID 718070 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][C@@H:15]3[CH2:17][C@H:12]2[CH2:13][N:14]3[C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl.[CH3:29]COCC>CO>[F:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][C@@H:15]3[CH2:17][C@H:12]2[CH2:13][N:14]3[C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=2)[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:29])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 67293124HCID 67293124, compound

Product 1

HCID 67006609methyl 2-fluoro-4-((1S,4S)-5-(3-(trifluoromethyl)phenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)benzoateYield 46.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirring solution of title compound 225 (250 mg 0.657 mmol), 2N HCl in ether (1 mL, 2.00 mmol) and methanol (25 mL) was refluxed over the weekend. The mixture was concentrated and the residue was purified by chromatography: 20 g SiO2, dry loaded on a samplet, 0% to 50% ethyl acetate in hexanes over 20 minutes to afford title compound 226 (120 mg, 46%) as a white foam. LRMS (ESI): (calc.) 394.13. (found) 395.3 (MH)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by chromatography
  3. dry with material20 g SiO2, dry loaded on a samplet, 0% to 50% ethyl acetate in hexanes over 20 minutes

Sources & evidence

ORD record
ord-824d670fc64b46aeb9ac14ed37b67b54
Source dataset
uspto-grants-2015_11
Patent number
US09193749B2

Reaction notes

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