Trifluoroacetic acid → HCID 86619856, compound

HRID 1943276Notes

Reaction equation

HRID 1943276 reaction equation
[CH:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:10]([CH:12]1[CH2:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)=[C:19]([F:29])[CH:18]=3)(O)[CH2:13]1)=[O:11])[CH2:2]2.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33]>ClCCCl>[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33].[CH:5]12[CH2:8][CH2:9][CH:1]([CH2:7][CH2:6]1)[CH2:2][N:3]([C:10]([CH:12]1[CH2:15][C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]4[CH2:25][CH2:26][CH2:27][CH2:28]4)=[C:19]([F:29])[CH:18]=3)=[CH:13]1)=[O:11])[CH2:4]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67278760HCID 67278760, compound2×

Product 1

HCID 86619856HCID 86619856, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of example 26, 3-aza-bicyclo[3.2.2]nonan-3-yl(3-(3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)-3-hydroxycyclobutyl)methanone (0.59 g, 1.48 mmol) in trifluoroaceticacid (2.5 mL) and 1,2-dichloroethane (16 mL) was refluxed for 20 h and concentrated to give crude 3-aza-bicyclo[3.2.2]nonan-3-yl(3-(3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)cyclobut-2-enyl)methanone trifluoroacetate salt as a dark purplish-brown oil, with residual TFA. This material was dissolved in EtOH (40 mL) and added to a hydrogenation bottle containing 10% palladium on carbon (93 mg) slurried in EtOH (˜3 mL). The mixture was shaken at room temperature under 48 psi of hydrogen for 2 h, filtered through diatomaceous earth with an EtOH rinse and concentrated to yield an orange oil. This was dissolved in EtOAc and washed with aqueous K2CO3 and brine, dried over MgSO4 and concentrated to afford 0.38 g of light orange oil. Flash chromatography on a 2″×3.5″ silica gel column flushing with 2% MeOH/EtOAc (500 mL) and then eluting with 500 ml each 5% and 10% MeOH/EtOAc afforded 0.256 g (45%) of the title compound as a light orange oil: Rf=0.21 (20% MeOH/EtOAc).

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-bf4dd7d3e61b4ed592fb101d0301630f
Source dataset
uspto-grants-2013_03
Patent number
US08389743B2

Reaction notes

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