1-Hydroxybenzotriazole → HCID 86656351, compound

HRID 1942467Notes

Reaction equation

HRID 1942467 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12]2[CH:13]=[C:14]([C:21](O)=[O:22])[C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=2[O:10][C:9]([CH3:25])([CH3:24])[C:8]1=[O:26].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[NH2:49][C@@H:50]1[CH2:55][CH2:54][CH2:53][N:52]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:51]1.S([O-])(O)(=O)=O.[Na+]>CN(C)C=O.C(N(CC)CC)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:12]2[CH:13]=[C:14]([C:21]([NH:49][C@@H:50]3[CH2:55][CH2:54][CH2:53][N:52]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:51]3)=[O:22])[C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=2[O:10][C:9]([CH3:24])([CH3:25])[C:8]1=[O:26]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516919Sodium BisulfateHCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 583758074-(4-Methoxybutyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid

Product 1

HCID 86656351HCID 86656351, compoundYield 764.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-(4-Methoxybutyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (100 mg) was dissolved in dimethylformamide (2 ml), and thereto were added 1-hydroxybenzotriazole (61.1 mg), 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (76.5 mg), triethylamine (55.6 μl) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (64.0 mg), and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added a 5% aqueous sodium hydrogen sulfate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a 5% aqueous sodium hydrogen sulfate solution, a saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the title compound (1136 mg) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with a 5% aqueous sodium hydrogen sulfate solution
  3. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-fec7598eeb8e401fa8db494b8065e12c
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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