Trifluoroacetic acid → HCID 86708515, compound

HRID 1430834Notes

Reaction equation

HRID 1430834 reaction equation
[NH2:1][C:2]1[C:3]([Cl:33])=[C:4]([N:10]2[CH2:15][CH2:14][C@@H:13]([N:16](C)[C:17](=O)OC(C)(C)C)[C@H:12]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:11]2)[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:1][C:2]1[CH:7]=[C:6]([CH:5]=[C:4]([N:10]2[CH2:15][CH2:14][C@@H:13]([NH:16][CH3:17])[C@H:12]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:11]2)[C:3]=1[Cl:33])[C:8]#[N:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86708516HCID 86708516, compound

Product 1

HCID 86708515HCID 86708515, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(+/−)-tert-butyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((tert-butyldimethylsilyl)oxy)piperidin-4-yl)(methyl)carbamate (Example 186B, 78 mg, 0.158 mmol) was treated with TFA (25% in 1,2-dichloroethane, 0.012 mL, 0.158 mmol) at rt for 1 h. LCMS showed completion of reaction. The reaction mixture was diluted with dichloromethane and washed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10). The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (12 g column, eluting with 1-10% 2 N ammonia in methanol/dichloromethane) to give (+/−)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-(methylamino)piperidin-1-yl)-4-chlorobenzonitrile (54 mg) was obtained as a colorless oil.

Workup

  1. customcompletion of reaction
  2. washwashed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe crude product was purified by flash chromatography on silica gel using
  7. washan automated ISCO system (12 g column, eluting with 1-10% 2 N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-c0d9e2f16d794168b24d833f99f55563
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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