Tetrahydrofuran → HCID 25211608, compound

HRID 1409826Notes

Reaction equation

HRID 1409826 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[C:19]([CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)#[N:20].C1COCC1.N1CCCCC1>C(N(CC)CC)C>[CH3:16][C:4]1[C:5]([C:8]2[S:12][C:11]([C:13]([N:24]3[CH2:25][CH2:26][CH:21]([C:19]#[N:20])[CH2:22][CH2:23]3)=[O:15])=[CH:10][CH:9]=2)=[N:6][O:7][C:3]=1[C:2]([F:1])([F:18])[F:17]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8082PiperidineHCID 1382234-CyanopiperidineHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25211608HCID 25211608, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 4-cyanopiperidine by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine and piperidine derivative. The reaction mixture was evaporated to a solid, triturated and filtered with the aid of water, then washed with a 1 N aqueous hydrochloric acid solution followed by water. The solid was air dried then chromatographed on a short column of silica gel with EtOAc as eluant to afford product as a colorless solid (91 mg, 61%). 1H NMR (CDCl3) 1.91-2.06 (m, 4 H), 2.37 (d, J=1.3, 3 H), 2.97-3.03 (m, 1 H), 3.71-3.79 (m, 2 H), 3.90-3.98 (m, 2 H), 7.34 (d, J=4.0, 1 H), 7.47 (d, J=4.0, 1 H). 13C NMR 7.9, 26.5, 28.9, 43.6, 114.8, 118.7 (q, J=271), 120.8, 128.1, 129.5, 131.7, 139.4, 155.2 (q, J=40), 157.8, 162.9. 19F NMR −63.2. LC/MS 6.18 min, [M+1]+ 370.

Workup

  1. customThe reaction mixture was evaporated to a solid
  2. customtriturated
  3. filtrationfiltered with the aid of water
  4. washwashed with a 1 N aqueous hydrochloric acid solution
  5. customdried
  6. customthen chromatographed on a short column of silica gel with EtOAc as eluant

Sources & evidence

ORD record
ord-36fd32b667d74552aa1efc65b1168890
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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