Piperidine → Piperidin-1-yl-[4-(5-trifluoromethyl-isoxazol-3-yl)-phenyl]-methanone

HRID 572272Notes

Reaction equation

HRID 572272 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH:4]=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>C1(C)C=CC=CC=1.C1COCC1.CN(C=O)C>[N:32]1([C:12]([C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)=[CH:16][CH:15]=2)=[O:14])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

8

Reactant 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 576061124-(5-(Trifluoromethyl)isoxazol-3-yl)benzoic acid

Product 1

HCID 57606102Piperidin-1-yl-[4-(5-trifluoromethyl-isoxazol-3-yl)-phenyl]-methanoneYield 91%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(5-Trifluoromethyl-isoxazol-3-yl)-benzoic acid (Preparative Example 11, 256 mg, 1.0 mmol) in toluene (10 mL) was treated with DMF (˜5 μL) followed by oxalyl chloride (112 μL, 1.3 mmol). The reaction was allowed to stir for 3 hr then concentrated in vacuo to afford crude acid chloride which was dissolved in THF (5 mL) and treated with a THF solution (2 mL) of triethylamine (174 μL, 1.25 mmol) and piperidine (109 μL, 1.1 mmol). The reaction was allowed to stir for 3 hr and concentrated in vacuo to afford crude product which was filtered with the aid of water and solids air dried to afford product as a colorless solid (295 mg, 91%). 1H NMR (CDCl3) 1.55-1.70 (m, 6H), 3.35 (br s, 2H), 3.73 (br s, 2H), 7.04 (s, 1H), 7.52 (d, J=8.3, 2H), 7.86 (d, J=7.9, 2H). 13C NMR 24.7, 25.8, 26.8, 43.4, 49.0, 103.7, 118.0 (q, J=270), 127.3, 127.9, 128.4, 139.2, 162.2, 169.4. 19F NMR −64.6. LC/MS 6.49 min, [M+1]+ 325.

Workup

  1. concentrationthen concentrated in vacuo
  2. customto afford crude acid chloride which
  3. stirringto stir for 3 hr
  4. concentrationconcentrated in vacuo
  5. customto afford crude product which
  6. filtrationwas filtered with the aid of water and solids air
  7. customdried

Sources & evidence

ORD record
ord-e0c7b538669048bbafc9a008e93bdc21
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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