Trifluoroacetic acid → HCID 131732379, compound

HRID 921646Notes

Reaction equation

HRID 921646 reaction equation
[Cl:1][C:2]1[C:7]([NH:8]C(OC(C)(C)C)=O)=[CH:6][C:5]([C:16]#[N:17])=[CH:4][C:3]=1[N:18]1[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:28])[O:26][CH3:27])[C@H:20]([O:29][Si:30]([CH:37]([CH3:39])[CH3:38])([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])[CH3:32])[CH2:19]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:8][C:7]1[C:2]([Cl:1])=[C:3]([N:18]2[CH2:23][CH2:22][C@@H:21]([NH:24][C:25](=[O:28])[O:26][CH3:27])[C@H:20]([O:29][Si:30]([CH:34]([CH3:36])[CH3:35])([CH:37]([CH3:39])[CH3:38])[CH:31]([CH3:33])[CH3:32])[CH2:19]2)[CH:4]=[C:5]([C:16]#[N:17])[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131732377HCID 131732377, compound

Product 1

HCID 131732379HCID 131732379, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl ((3R,4R)-1-(2-chloro-5-cyano-3-(N-Boc-amino)phenyl)-3-((triisopropylsilyl)oxy)piperidin-4-yl)carbamate (242 mg, 0.354 mmol) was treated with TFA (25% in 1,2-dichloroethane, 4 mL, 12.98 mmol) at room temperature for 1 h. 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 (40 g column, eluting with 0-20% ethyl acetate/dichloromethane). Methyl ((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-((triisopropylsilyl)oxy)piperidin-4-yl)carbamate (135 mg) was obtained as a white solid.

Workup

  1. washwashed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10)
  2. dry with materialthe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customthe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (40 g column, eluting with 0-20% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-45960db64ad24bbeb8472da2517ad5a0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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