Trifluoroacetic acid → HCID 90370295, compound

HRID 2176023Notes

Reaction equation

HRID 2176023 reaction equation
[CH3:1][CH2:2][CH:3]([NH:6][CH2:7][C:8]1[CH:9]=[C:10]([CH:30]=[CH:31][CH:32]=1)[C:11]([NH:13][C:14]1[S:15][C:16]2[CH2:29][CH2:28][CH2:27][CH2:26][C:17]=2[C:18]=1[C:19]([O:21]C(C)(C)C)=[O:20])=O)[CH2:4][CH3:5].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:5][CH2:4][CH:3]([NH:6][CH2:7][C:8]1[CH:9]=[C:10]([C:11]2[O:21][C:19](=[O:20])[C:18]3[C:17]4[CH2:26][CH2:27][CH2:28][CH2:29][C:16]=4[S:15][C:14]=3[N:13]=2)[CH:30]=[CH:31][CH:32]=1)[CH2:2][CH3:1]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90370131HCID 90370131, compound

Product 1

HCID 90370295HCID 90370295, compoundYield 93.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 8.99 g of tert-butyl 2-({3-[(pentan-3-ylamino)methyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate and 100 mL of methylene chloride was added 30 mL of TFA, followed by stirring for 15 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and azeotropy was performed using toluene. 4.3 mL of thionyl chloride and 50 mL of toluene were added to the residue, and 0.10 mL of DMF was added dropwise thereto, followed by stirring for 1 hour at 60° C. The reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brined and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2), thereby obtaining 7.05 g of 2-{3-[(pentan-3-ylamino)methyl]phenyl}-5,6,7,8-tetrahydro-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and azeotropy
  2. addition4.3 mL of thionyl chloride and 50 mL of toluene were added to the residue, and 0.10 mL of DMF
  3. additionwas added dropwise
  4. stirringby stirring for 1 hour at 60° C
  5. concentrationThe reaction mixture was concentrated under reduced pressure
  6. additiona saturated aqueous sodium hydrogen carbonate solution was added
  7. extractionfollowed by extraction with ethyl acetate
  8. washThe organic layer was washed with saturated brined and
  9. dry with materialdried over anhydrous sodium sulfate
  10. customthe solvent was removed under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2)

Sources & evidence

ORD record
ord-cf792b67c6194dd58ab459158576050e
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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