Acetonitrile → Trifluoroacetic acid

HRID 2405024Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][O:21]S(C2C=CC(C)=CC=2)(=O)=O)[CH2:10][CH2:9]1)=O)(C)(C)C.CC#N.C([O-])([O-])=O.[K+].[K+].[F:41][C:42]1[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[C:43]=1O.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]>CC(O)=O.O>[F:41][C:42]1[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[C:43]=1[O:21][CH2:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1.[C:51]([OH:57])([C:53]([F:56])([F:55])[F:54])=[O:52]

Participants

Conditions

Temperature: 50 °C

Procedure

4-[2-(Toluene-4-sulfonyloxymethyl)phenyl]piperidine-1-carboxylic acid t-butyl ester (2.1 g, 4.7 mmol, 1.0 eq.) was dissolved in MeCN (46 mL, 890 mmol) and added to K2CO3 (1.9 g, 14 mmol, 3.0 eq.) and 2,4,6-trifluorophenol (1.0 g, 7.0 mmol, 1.5 eq.). The mixture was shaken at 50° C. overnight, then cooled to room temperature. The supernatant was separated from the K2CO3 and other solids. TFA (7 mL, 90 mmol, 20.0 eq.) was added to the supernatant and the mixture was shaken overnight at room temperature. The solution was then concentrated to yield a crude residue. The residue was dissolved in 5.0 mL 1:1 AcOH/H2O, then in an additional 2.0 mL AcOH, filtered and purified by preparative HPLC to yield the title compound as a TFA salt (1.3 g, 97.5% purity). MS m/z: [M+H]+ calcd for C18H18F3NO, 322.13. found 322.2.

Workup

temperaturecooled to room temperature
customThe supernatant was separated from the K2CO3 and other solids
stirringthe mixture was shaken overnight at room temperature
concentrationThe solution was then concentrated
customto yield a crude residue
filtrationin an additional 2.0 mL AcOH, filtered
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-fcfd5b55474c4d43a596dce07a7595b5
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802857B2

Reaction notes

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