Trifluoroacetic acid → HCID 118307945, compound
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]C(=O)OC(C)(C)C)=[CH:4][C:3]=1[C@:16]1([CH3:27])[C:21]([F:23])([F:22])[CH2:20][C@:19]([F:25])([CH3:24])[C:18](=[S:26])[NH:17]1.C(O)(C(F)(F)F)=O>ClCCl.C1(C)C=CC=CC=1>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C@@:16]2([CH3:27])[NH:17][C:18](=[S:26])[C@@:19]([F:25])([CH3:24])[CH2:20][C:21]2([F:23])[F:22])[CH:4]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 0 °C
Procedure
tert-butyl (4-fluoro-3-((2R,5R)-3,3,5-trifluoro-2,5-dimethyl-6-thioxopiperidin-2-yl)phenyl)carbamate (816 mg, 2.01 mmol) was dissolved in dichloromethane (9.2 mL). The solution was cooled to 0° C. and TFA (4.6 mL, 59.5 mmol) was added. The solution was stirred at 0° C. for 1 h 20 min. The reaction was diluted with toluene (15 mL) and concentrated to approx. 10 mL under reduced pressure. The residue was diluted with ethyl acetate (50 mL) and washed with saturated aqueous NaHCO3 (25 mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organics were dried over MgSO4, filtered, and concentrated under reduced pressure to afford (3R,6R)-6-(5-amino-2-fluorophenyl)-3,5,5-trifluoro-3,6-dimethylpiperidine-2-thione (587 mg, (50% purity), 47.7% yield). The material was used in the next reaction step without further purification.
Workup
- concentrationconcentrated to approx. 10 mL under reduced pressure
- additionThe residue was diluted with ethyl acetate (50 mL)
- washwashed with saturated aqueous NaHCO3 (25 mL)
- customThe phases were separated
- extractionthe aqueous layer was extracted with ethyl acetate (2×25 mL)
- dry with materialThe combined organics were dried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-3162de917abc4f3a8a0130c05d5fe366
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09353084B2
Reaction notes
Loading…