Tetrahydrofuran → [5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-morpholin-4-yl-methanone

HRID 572302Notes

Reaction equation

HRID 572302 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].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C1COCC1.N1CCCCC1>C(N(CC)CC)C>[CH3:16][C:4]1[C:5]([C:8]2[S:12][C:11]([C:13]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]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 8083MorpholineHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25211607[5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophen-2-yl]-morpholin-4-yl-methanoneYield 95%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and morpholine 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 to afford product as a colorless solid (66 mg, 95%). 1H NMR (CDCl3) 2.34 (d, J=1.3, 3H), 3.71-3.77 (m, 8H), 7.32 (d, J=4.0, 1H), 7.43 (d, J=4.0, 1H). 13C NMR 7.9, ˜48 (br), 67.0, 114.7, 118.7 (q, J=271), 128.0, 129.5, 131.7, 139.5, 157.9, 162.8. 19F NMR −63.2. LC/MS 5.93 min, [M+1]+ 347.

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

Sources & evidence

ORD record
ord-4f3955a6f9624be0abc4ddedce7501b6
Source dataset
uspto-grants-2015_05
Patent number
US09029397B2

Reaction notes

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