Trifluoroacetic acid → HCID 10167188, compound

HRID 1370998Notes

Reaction equation

HRID 1370998 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[O:17][N:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[O:31]1C[CH:32]1[CH2:34][N:35]1[C:43]2[CH2:42][CH2:41][N:40]([C:44](=[O:46])[CH3:45])[CH2:39][C:38]=2[C:37]([C:47]2[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=2)=[N:36]1>C(Cl)Cl>[O:17]1[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:15]([O:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:6][CH:32]([OH:31])[CH2:34][N:35]3[C:43]4[CH2:42][CH2:41][N:40]([C:44](=[O:46])[CH3:45])[CH2:39][C:38]=4[C:37]([C:47]4[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=4)=[N:36]3)[CH2:13][CH2:12]2)=[N:16]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 222938171-[1-Oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanoneHCID 691580111,1-Dimethylethyl 4-(1,2-benzisoxazol-3-yloxy)-1-piperidinecarboxylate

Product 1

HCID 10167188HCID 10167188, compoundYield 68.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 176 mg (0.55 mmol) of 4-(benzo[d]isoxazol-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester in CH2Cl2(2 mL) was treated with trifluoroacetic acid (0.5 mL) at room temperature overnight. The solvent was then removed and the crude product dissolved in methanol and stirred over 100 mg of sodium bicarbonate for 1 h, the solid was then filtered off and the filtrate concentrated. The crude piperidine was then dissolved in 4 mL EtOH and treated with 202 mg (0.55 mmol) of 1-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone The solution was heated to 60° C. overnight. The solvent was then removed by rotary evaporation and the crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc) to afford 220 mg (68%) of a white solid. MS (electrospray): exact mass calculated for C30H32F3N5O4, 583.24; m/z found, 584.2 [M+H]+. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.77 (d, J=8.22 Hz, 1H), 7.69 (m, 2H), 7.66-7.61 (m, 2H), 7.54-7.49 (m, 1H), 7.41 (d, J=8.41 Hz, 1H), 7.28-7.23 (m, 1H), 4.93 (br m, 1H), 4.88 and 4.75 (A and B of AB quartet, J=15.65 Hz, 1H), 4.65 (br s, 1H), 4.24-4.18 (m, 0.75H), 4.18-4.09 (m, 1.25H), 4.07-3.98 (m, 1.5H), 3.91-3.79 (m, 0.5H), 3.79-3.67 (m, 1H), 3.02-2.85 (m, 2.4H), 2.85-2.70 (m, 1.6H), 2.61-2.52 (m, 1H), 2.51-2.40 (m, 2H), 2.39-2.30 (m, 1H), 2.24-2.12 (br m, 2H), 2.20 (s, 1.5H), 2.16 (s, 1.5H), 2.02-1.86 (m, 2H).

Workup

  1. customThe solvent was then removed
  2. dissolutionthe crude product dissolved in methanol
  3. filtrationthe solid was then filtered off
  4. concentrationthe filtrate concentrated
  5. dissolutionThe crude piperidine was then dissolved in 4 mL EtOH
  6. customThe solvent was then removed by rotary evaporation
  7. customthe crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-5d947c7b2ab94199abc1e9f772afe0e9
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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