Trifluoroacetic acid → HCID 57797482, compound

HRID 2101192Notes

Reaction equation

HRID 2101192 reaction equation
CO[C:3](=[O:24])[C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[F:18])[CH:7]=[CH:6][C:5]=1[CH:19]=[CH:20]OCC.C(O)(C(F)(F)F)=O.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([O:45][CH2:46][CH:47]([NH2:51])[CH:48]([CH3:50])[CH3:49])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[C:32]([O:36][C:37]([N:39]1[CH2:40][CH2:41][CH:42]([O:45][CH2:46][CH:47]([N:51]2[CH2:20][CH2:19][C:5]3[C:4](=[CH:9][C:8]([O:10][C:11]4[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=4[F:18])=[CH:7][CH:6]=3)[C:3]2=[O:24])[CH:48]([CH3:49])[CH3:50])[CH2:43][CH2:44]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 57797621HCID 57797621, compoundHCID 68827789HCID 68827789, compound

Product 1

HCID 57797482HCID 57797482, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To the solution of 5-(2,4-difluoro-phenoxy)-2-(2-ethoxy-vinyl)-benzoic acid methyl ester 9 (194 mg, 0.6 mmol) in dichloromethane (5 mL) was added 1 mL of TFA and five drops of water. The reaction was stirred at room temperature for ten minutes, at which time the solvent was removed. The reaction mixture was re-suspended in dichloroethane and 4-(2-amino-3-methyl-butoxy)-piperidine-1-carboxylic acid tert-butyl ester A11 (200 mg, 0.70 mmol), DIEA (154 mL, 0.87 mmol), and sodium triacetoxyborohydride (184 mg, 1.87 mmol) were added. The mixture was stirred at room temperature for fifteen minutes and then at 60° C. for additional 16 hours. The reaction was diluted with 100 mL CH2Cl2 and extracted with saturated brine (100 mL). The organic layer was concentrated and loaded onto a silica gel column and eluted with 2% methanol in dichloromethane to give 250 mg (79%) of 4-{2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butoxy}-piperidine-1-carboxylic acid tert-butyl ester 15 as light yellow solid. TLC, Rf=0.3 (2% MeOH CH2Cl2). 1H NMR (CDCl3) δ 0.92 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.5 Hz, 3H), 1.31 (m, 1H), 1.44 (s, 9H), 1.61 (m, 2H), 2.2 (m, 1H), 2.90 (m, 2H), 3.14 (m, 2H), 3.41(m, 1H), 3.51 (m, 1H), 3.73 (m, 1H), 2.63 (m, 4H), 4.02 (m, 1H), 4.56 (m, 1H), 6,84 (m, 1H), 6.93 (m, 1H), 7.06 (m, 2H), 7.14 (d, J=8.1 Hz, 1H), 7.54 (d, J=2.6 Hz, 1H), M+1 found 545.3; C30H38F2N2O5 requires 544.27.

Workup

  1. customwas removed
  2. stirringThe mixture was stirred at room temperature for fifteen minutes
  3. extractionextracted with saturated brine (100 mL)
  4. concentrationThe organic layer was concentrated
  5. washeluted with 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-a408c550605b43c98a56bb8b9ed0e3c2
Source dataset
uspto-grants-2009_08
Patent number
US07572783B2

Reaction notes

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