Trifluoroacetic acid → HCID 68829327, compound

HRID 2101191Notes

Reaction equation

HRID 2101191 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.Cl.[C:33]([O:37][C:38](=[O:44])[C@@H:39]([CH:41]([CH3:43])[CH3:42])[NH2:40])([CH3:36])([CH3:35])[CH3:34].C(N(CC)CC)C>ClC(Cl)C.O.ClCCl>[C:33]([O:37][C:38](=[O:44])[CH:39]([N:40]1[CH2:20][CH2:19][C:5]2[C:4](=[CH:9][C:8]([O:10][C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])=[CH:7][CH:6]=2)[C:3]1=[O:24])[CH:41]([CH3:42])[CH3:43])([CH3:35])([CH3:34])[CH3:36]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 45108216H-D-Val-OtBu hydrochlorideHCID 68827789HCID 68827789, compound

Product 1

HCID 68829327HCID 68829327, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of 5-(2,4-difluoro-phenoxy)-2-(2-ethoxy-vinyl)-benzoic acid methyl ester 9 (1.2 g, 3.8 mmol) in dichloroethane (20 mL) was added 5 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 crude reaction mixture was re-suspended in dichloroethane and D-valine t-butylester HCl (2.05 g, 9.75 mmol), triethylamine (1.36 mL, 9.75 mmol), and tiacetoxyborohydride (2.76 g, 13 mmol) were added. The reaction was stirred at room temperature for fifteen minutes and then at 60° C. for an additional 16 hours. The mixture was diluted with 100 mL dichloromethane and extracted with saturated brine (100 mL). The organic layer was concentrated, loaded onto a silica gel column and eluted with dichloromethane to yield 516 mg (77%) of 2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butyric acid tert-butyl ester 10 as a light yellow solid. TLC, Rf=0.3 (2% MeOH CH2Cl2); 1H NMR (CDCl3) δ 0.93 (d, J=6.7 Hz, 3H), 1.05 (d, J=6.6 Hz, 3H), 1.45 (s, 9H), 2.24 (m, 1H), 2.93 (m, 2H), 3.52 (m, 1H), 3.75 (m, 1H), 5.00 (d, J=6.7 Hz, 1H), 6.85 (m, 1H), 6.93 (m, 1H), 7.07 (m, 2H), 7.15 (d, J=8.3 Hz, 1H), 7.58 (d, J=2.6 Hz, 1H). M+1 found 432.10; C24H27F2NO4 requires 431.19.

Workup

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

Sources & evidence

ORD record
ord-ec721caea8294d4092a40940c9bc061a
Source dataset
uspto-grants-2009_08
Patent number
US07572783B2

Reaction notes

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