Hydrochloric Acid → HCID 131729819, compound

HRID 1409807Notes

Reaction equation

HRID 1409807 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].C([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)(OC(C)(C)C)=O.[ClH:32]>O1CCOCC1>[ClH:32].[CH3:1][C:2]1[C:3]([C:11]2[S:15][C:14]([C:16]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[O:18])=[CH:13][CH:12]=2)=[N:4][O:5][C:6]=1[C:7]([F:8])([F:9])[F:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 131729819HCID 131729819, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Prepared from 5-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and N-Boc-piperazine by the method described in Example 2 Method B. 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 silica gel with EtOAc/hexanes (50%) as eluant to afford intermediate N-Boc protected product as a colorless solid (165 mg, 74%). The Boc-protected intermediate was dissolved in 1,4-dioxane (5 mL) and treated with a 4 N solution of hydrogen chloride in 1,4-dioxane and stirred for 12 hr, after which time the reaction mixture was evaporated to approximately ½ volume and diluted with ethyl ether (20 mL). The resulting solids were filtered and air dried to afford product as a colorless solid (131 mg, 69% overall). 1H NMR (D2O) 2.16 (s, 3 H), 3.22 (m, 4 H), 3.87 (m, 4 H), 7.34 (d, J=4.0, 1 H), 7.42 (d, J=4.0, 1 H). 19F NMR −63.6. LC/MS 4.34 min, [M+1]+ 346.

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 silica gel with EtOAc/hexanes (50%) as eluant
  7. customto afford intermediate N-Boc protected product as a colorless solid (165 mg, 74%)
  8. customafter which time the reaction mixture was evaporated to approximately ½ volume
  9. additiondiluted with ethyl ether (20 mL)
  10. filtrationThe resulting solids were filtered
  11. customair dried

Sources & evidence

ORD record
ord-f0fb8b644d944ce9b109de8e36aa8415
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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