Tetrahydrofuran → HCID 25211284, compound

HRID 1409809Notes

Reaction equation

HRID 1409809 reaction equation
[CH3:1][C:2]1[C:3]([C:11]2[S:15][C:14]([C:16]([OH:18])=O)=[CH:13][CH:12]=2)=[N:4][O:5][C:6]=1[C:7]([F:10])([F:9])[F:8].Cl.[F:20][C:21]1([F:25])[CH2:24][NH:23][CH2:22]1.C1COCC1.N1CCC1>C(N(CC)CC)C>[F:20][C:21]1([F:25])[CH2:24][N:23]([C:16]([C:14]2[S:15][C:11]([C:3]3[C:2]([CH3:1])=[C:6]([C:7]([F:8])([F:9])[F:10])[O:5][N:4]=3)=[CH:12][CH:13]=2)=[O:18])[CH2:22]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10422AzetidineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 25211284HCID 25211284, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and 3,3-difluoroazetidine hydrochloride 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 (containing and additional 1.1 eq to neutralize the azetadinyl hydrochloride salt) and azetidine 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 and then chromatographed on silica gel with EtOAc/hexanes (25 then 50%) as eluant to afford product as a colorless solid (43 mg, 49%). 1H NMR (CDCl3) 2.37 (s, 3 H), 4.68 (br, 4 H), 4.19 (br, 2 H), 7.53 (s, 2 H). 19F NMR −100.6, −63.1. LC/MS 6.42 min, [M+1]+ 353.

Workup

  1. additioncontaining
  2. customThe reaction mixture was evaporated to a solid
  3. customtriturated
  4. filtrationfiltered with the aid of water
  5. washwashed with a 1 N aqueous hydrochloric acid solution
  6. customdried
  7. customchromatographed on silica gel with EtOAc/hexanes (25

Sources & evidence

ORD record
ord-9439f3e940804b2ba8ec0fe94415bcef
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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