Trifluoroacetic acid → HCID 86698440, compound

HRID 527606Notes

Reaction equation

HRID 527606 reaction equation
CC([N:5]([C@@:9]([CH3:34])([C:12]([NH:14][C:15]1[CH:16]=[N:17][C:18]([O:21][C:22]2[C:27]3[C:28]4([CH2:31][O:32][CH2:33][C:26]=3[CH:25]=[CH:24][CH:23]=2)[CH2:30][CH2:29]4)=[CH:19][CH:20]=1)=[O:13])[CH2:10][CH3:11])C(=O)[O-])(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[C:28]12([C:27]3[C:22]([O:21][C:18]4[N:17]=[CH:16][C:15]([NH:14][C:12](=[O:13])[C@:9]([CH3:34])([CH2:10][CH3:11])[NH2:5])=[CH:20][CH:19]=4)=[CH:23][CH:24]=[CH:25][C:26]=3[CH2:33][O:32][CH2:31]1)[CH2:29][CH2:30]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86698441HCID 86698441, compound2×

Product 1

HCID 86698440HCID 86698440, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1,1-dimethylethyl[(1R)-1-methyl-1-({[6-(1H-spiro[2-benzopyran-4,1′-cyclopropan]-5-yloxy)-3-pyridinyl]amino}carbonyl)propyl]carbamate (Intermediate 140, 62 mg) in dry dichloromethane (6 mL) at 0° C. TFA (2 ml, 26.0 mmol) was slowly added and the reaction mixture was stirred for 3 hours at the same temperature. The reaction mixture was diluted with dichloromethane (15 ml) and an aqueous saturated solution of NaHCO3 was added while the pH was allowed to reach ˜8. Two phases were separated and the organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and dichloromethane/methanol as eluents from 99:1 to 95:5. This afforded the title compound as a white solid (42 mg, 86% yield).

Workup

  1. customat 0° C
  2. customTwo phases were separated
  3. dry with materialthe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and dichloromethane/methanol as eluents from 99:1 to 95:5

Sources & evidence

ORD record
ord-0ba6c7d8db74414e8068b34e9f80a2df
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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