Trifluoroacetic acid → rac-4-chloro-2-(trans-2-hydroxycyclohexyl)-5-methoxy-6-(4-(1H-pyrazol-1-yl)benzyl)isoindolin-1-one

HRID 629388Notes

Reaction equation

HRID 629388 reaction equation
[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:24]=[CH:23][CH:22]=[N:21]3)=[CH:16][CH:15]=2)[CH:8]=[C:7]2[C:3]=1[CH:4](O)[N:5]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[OH:32])[C:6]2=[O:25].FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH:24]=[CH:23][CH:22]=[N:21]3)=[CH:16][CH:15]=2)[CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[OH:32])[C:6]2=[O:25]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 118468437rac-4-chloro-3-hydroxy-2-(trans-2-hydroxycyclohexyl)-5-methoxy-6-[4-(1H-pyrazol-1-yl)benzyl]-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 118468217rac-4-chloro-2-(trans-2-hydroxycyclohexyl)-5-methoxy-6-(4-(1H-pyrazol-1-yl)benzyl)isoindolin-1-oneYield 29.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of rac-4-chloro-3-hydroxy-2-(trans-2-hydroxycyclohexyl)-5-methoxy-6-[4-(1H-pyrazol-1-yl)benzyl]-2,3-dihydro-1H-isoindol-1-one (0.07 g) in dichloromethane (2.00 mL) was added trifluoroacetic acid (0.50 mL) under ice-cooling, and the mixture was stirred for 15 min. Then, triethylsilane (0.40 mL) was added thereto, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (×2). The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by prep-HPLC, then lyophilized to give the title compound (0.02 g).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate (×2)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by prep-HPLC,

Sources & evidence

ORD record
ord-75a7cb91a8f945ac9db83ce70d5911b1
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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