Hydrochloric Acid → HCID 131729828, compound

HRID 1409853Notes

Reaction equation

HRID 1409853 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].CC1C(C2SC(C(N3CCC[C@@H](NC(=O)C)C3)=O)=CC=2)=NOC=1C(F)(F)F.[CH3:46][N:47]([CH2:55][C@@H:56]1[CH2:61][CH2:60][CH2:59][NH:58][CH2:57]1)C(=O)OC(C)(C)C.[ClH:62]>O1CCOCC1.C(N(CC)CC)C.C1COCC1>[ClH:62].[CH3:46][NH:47][CH2:55][C@@H:56]1[CH2:61][CH2:60][CH2:59][N:58]([C:13]([C:11]2[S:12][C:8]([C:5]3[C:4]([CH3:16])=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:57]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 252109975-(4-Methyl-5-trifluoromethyl-isoxazol-3-yl)-thiophene-2-carboxylic acidHCID 25211385HCID 25211385, compoundHCID 269669601124199-21-8

Product 1

HCID 131729828HCID 131729828, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Procedure

Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and tert-butyl methyl[(3R)-piperidin-3-ylmethyl]carbamate (Preparative Example 33, 298 mg, 1.30 mmol) by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride (0.90 eq) was added to a THF solution of triethylamine and tert-butyl methyl[(3R)-piperidin-3-ylmethyl]carbamate. The reaction was allowed to stir 4 hr then partitioned between EtOAc (10 mL) and a 1 N aqueous HCl solution (10 mL). The organic portion was washed with a further portion of 1N HCl solution (10 mL) followed by a saturated aqueous NaHCO3 solution (10 mL) and brine (10 mL). The organic layer was then dried over MgSO4, filtered, and evaporated to a residue that was chromatographed on silica gel with EtOAc/hexane (40% then 60%) as eluant to afford Boc-protected intermediate as a yellow-tinted oil (423 mg, 67%). LC/MS 7.44 min, [M+1]+ 487. The intermediate was then treated with a 4 N solution of hydrogen chloride in 1,4-dioxane (4 mL) and stirred for 24 hr, after which time the reaction mixture was evaporated in vacuo to afford a free-flowing colorless powder (320 mg, 88%). LC/MS 4.91 min, [M+1]+ 388.

Workup

  1. customthen partitioned between EtOAc (10 mL)
  2. washThe organic portion was washed with a further portion of 1N HCl solution (10 mL)
  3. dry with materialThe organic layer was then dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to a residue that
  6. customwas chromatographed on silica gel with EtOAc/hexane (40%
  7. custom60%) as eluant to afford Boc-
  8. customLC/MS 7.44 min, [M+1]+ 487
  9. stirringstirred for 24 hr
  10. customafter which time the reaction mixture was evaporated in vacuo

Sources & evidence

ORD record
ord-d1ed9f7a67fb4e168e48c0199e98fc90
Source dataset
uspto-grants-2014_12
Patent number
US08921399B2

Reaction notes

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