Water → HCID 58696252, compound

HRID 1178338Notes

Reaction equation

HRID 1178338 reaction equation
O.ON1C2C=CC=CC=2N=N1.[F:12][C:13]([F:19])([F:18])[CH2:14][C:15](O)=[O:16].[C:20]([O:24][C:25](=[O:43])[N:26]([C@:28]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([Cl:42])[CH:36]=1)([CH2:32][CH:33]=[CH2:34])[CH2:29][NH:30][CH3:31])[CH3:27])([CH3:23])([CH3:22])[CH3:21].O>O1CCCC1>[C:20]([O:24][C:25](=[O:43])[N:26]([C@:28]([C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([Cl:42])[CH:36]=1)([CH2:32][CH:33]=[CH2:34])[CH2:29][N:30]([CH3:31])[C:15](=[O:16])[CH2:14][C:13]([F:19])([F:18])[F:12])[CH3:27])([CH3:21])([CH3:22])[CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 27779723,3,3-Trifluoropropionic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 58696292HCID 58696292, compound

Product 1

HCID 58696252HCID 58696252, compoundYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-Hydroxybenzotriazole monohydrate (11.5 g) was dissolved in anhydrous tetrahydrofuran (0.8 L). At room temperature, 3,3,3-trifluoropropionic acid (120.3 g) was added thereto. Under cooling with ice, 1-[3-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (180.0 g) was added to the mixture, and the resultant mixture was stirred for 10 minutes at the same temperature. A solution of tert-butyl[2-(S)-(3,4-dichlorophenyl)-1-methylamino(4-penten-2-yl)]methylcarbamate (318.8 g) in anhydrous tetrahydrofuran (0.9 L) was added thereto, and the mixture was stirred for 2 hours at room temperature. The reaction mixture was poured into water, extracted with ethyl acetate, sequentially washed with water, aqueous citric acid, saturated aqueous sodium bicarbonate, and saturated brine, and dried over sodium sulfate anhydrate. The solvent was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1 to 5:1 to 2:1 to 1:1), to thereby give the title compound (275.7 g, 69.7%, 5 steps).

Workup

  1. additionwas added to the mixture
  2. extractionextracted with ethyl acetate
  3. washsequentially washed with water, aqueous citric acid, saturated aqueous sodium bicarbonate, and saturated brine
  4. dry with materialdried over sodium sulfate anhydrate
  5. concentrationThe solvent was concentrated under reduced pressure
  6. customthe residue was purified through silica gel column chromatography (n-hexane:ethyl acetate=6:1 to 5:1 to 2:1 to 1:1)

Sources & evidence

ORD record
ord-76e71443cba145e4af3378626d1a1247
Source dataset
uspto-grants-2007_10
Patent number
US07276511B2

Reaction notes

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