Trifluoroacetic acid → HCID 67572480, compound

HRID 1292700Notes

Reaction equation

HRID 1292700 reaction equation
C(O[C:6]([NH:8][C@@H:9]([CH2:30][CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])[CH2:10][N:11]([C:20]([O:22][CH2:23]C1C=CC=CC=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=1)=O)(C)(C)C.F[C:37](F)(F)[C:38](O)=O.C(O[BH-](O[C:53](=O)[CH3:54])OC(=O)C)(=O)C.[Na+].[C:57]1([CH2:67][NH:68][CH2:69][C@@H:70]([NH:75][C:76](OC(C)(C)C)=O)[C@@H](C)CC)[C:66]2[C:61](=CC=CC=2)[CH:60]=[CH:59][CH:58]=1.[CH3:83][N:84]1CCOCC1.[CH3:90][CH2:91]OC(C)=O>ClCCl>[C:83]([C:60]1[CH:59]=[CH:58][C:57]([CH2:67][N:68]2[C:69]([CH2:6][NH:8][C@@H:9]([CH2:30][CH2:31][S:32]([CH3:35])(=[O:34])=[O:33])[CH2:10][N:11]([C:20]([O:22][CH2:23][C:38]3[CH:37]=[CH:54][CH:53]=[CH:91][CH:90]=3)=[O:21])[CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=3)=[CH:70][N:75]=[CH:76]2)=[CH:66][CH:61]=1)#[N:84]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 18660163HCID 18660163, compoundHCID 53852682HCID 53852682, compound

Product 1

HCID 67572480HCID 67572480, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Step E (360 mg, 0.686 mmol) in 6 mL of dichloromethane was added at room temperature dropwise 3 mL of trifluoroacetic acid. After 30 minutes, the solution was concentrated in vacuo. The resulting product was reconcentrated from benzene three times to remove excess trifluoroacetic acid. To a solution of the amine salt in 4.2 mL of 1,2-dichloroethane at 0° C. was added 4 Å powdered molecular sieves, followed by sodium triacetoxyborohydride (363 mg, 1.71 mmol). The aldehyde from Step E of Example 1 (159 mg, 0.754 mmol) was added at 0° C., followed by N-methylmorpholine (0.076 mL, 0.69 mmol). The reaction was stirred overnight, allowing it to warm to room temperature. The reaction was poured into EtOAc, washed with sat. aq. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting product was purified by silica gel chromatography (50-75% acetone/hexane) to provide the desired product. A portion of this was taken up in CH2Cl2 and treated with excess HCl/Et2O, then stripped to provide the titled compound.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. customto remove excess trifluoroacetic acid
  3. additionTo a solution of the amine salt in 4.2 mL of 1,2-dichloroethane at 0° C. was added 4 Å
  4. washwashed with sat. aq. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting product was purified by silica gel chromatography (50-75% acetone/hexane)

Sources & evidence

ORD record
ord-0eef85d0856a40648df339d85d6e1fdf
Source dataset
uspto-grants-1998_05
Patent number
US05756528

Reaction notes

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