Hydrochloric Acid → HCID 131729820, compound

HRID 1409812Notes

Reaction equation

HRID 1409812 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][CH2:29][C@H:28]([NH2:32])[CH2:27]1)(OC(C)(C)C)=O.[ClH:33]>O1CCOCC1>[ClH:33].[NH2:32][C@H:28]1[CH2:29][CH2:30][CH2:31][N:26]([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])[CH2:27]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylateHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acid

Product 1

HCID 131729820HCID 131729820, compoundYield 71%

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-3-(S)-aminopiperidine 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 then 75%) as eluant to afford intermediate N-Boc protected product as a colorless solid (87 mg, 76%). 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 (70 mg, 71% overall). 1H NMR (D2O) 1.36 (m, 1 H), 1.58 (m, 2 H), 1.90 (s, 3 H), 1.96 (m, 1 H), 3.08 (m, 3 H), 3.21 (m, 1 H), 3.65 (m, 1H), 4.18 (br d, J=11.4, 1 H), 7.06 (br d, 1 H), 7.09 (br d, 1H). 19F NMR −64.6. LC/MS 4.40 min, [M+1]+ 360.

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
  7. custom75%) as eluant to afford intermediate N-Boc protected product as a colorless solid (87 mg, 76%)
  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-eb54403fb39d4d1e822ac2866f38fb5e
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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