Ammonium Chloride → HCID 67332148, compound

HRID 1942511Notes

Reaction equation

HRID 1942511 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].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:49][C@@H:50]1[C@H:55]([C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=2)[CH2:54][CH2:53][N:52]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:51]1.[Cl-].[NH4+]>CN(C=O)C.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[C@H:55]([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[CH2:54][CH2:53][N:52]([C:62]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:63])[CH2:51]3)=[O:22])[C:15]([C:17]([F:19])([F:18])[F:20])=[CH:16][C:11]=2[O:10][C:9]([CH3:25])([CH3:24])[C:8]1=[O:26]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 25324002HCID 25324002, compoundHCID 583758074-(4-Methoxybutyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid

Product 1

HCID 67332148HCID 67332148, compoundYield 100.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-(4-methoxybutyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (739 mg) in DMF (5 ml) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (755 mg), 1-hydroxybenzotriazole (532 mg), triethylamine (549 μl), tert-butyl (3R,4S)-3-amino-4-phenylpiperidine-1-carboxylate (653 mg), and the mixture was stirred at room temperature for 3 hours. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous ammonium chloride solution, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (the developing solvent: hexane/ethyl acetate=3/1) to give the title compound (1.25 g).

Workup

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

Sources & evidence

ORD record
ord-17be4340bcc0484087ba165b8739be1f
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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