Triethylamine → HCID 86665014, compound

HRID 244378Notes

Reaction equation

HRID 244378 reaction equation
[CH2:1]([N:8]([CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)[CH2:9][CH2:10][N:11]1[C:16]2[CH:17]=[C:18]([C:22](=[O:40])[N:23]([C@@H:27]3[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:28]3)[CH:24]([CH3:26])[CH3:25])[C:19]([CH3:21])=[CH:20][C:15]=2[O:14][C:13]([CH3:44])([C:41](O)=[O:42])[C:12]1=[O:45])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(OC(Cl)=O)C(C)C>O1CCCC1>[CH2:1]([N:8]([CH2:46][C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1)[CH2:9][CH2:10][N:11]1[C:16]2[CH:17]=[C:18]([C:22]([N:23]([CH:24]([CH3:25])[CH3:26])[C@@H:27]3[CH2:32][CH2:31][CH2:30][N:29]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])[CH2:28]3)=[O:40])[C:19]([CH3:21])=[CH:20][C:15]=2[O:14][C:13]([CH2:41][OH:42])([CH3:44])[C:12]1=[O:45])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 67512141HCID 67512141, compound

Product 1

HCID 86665014HCID 86665014, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen atmosphere, the mixture was cooled with ice-bath, and to a solution of the obtained 4-[2-(dibenzylamino)ethyl]-2,7-dimethyl-6-{[(3R)-1-{[(2-methyl-2-propanyl)oxy]carbonyl}-3-piperidinyl](2-propanyl)carbamoyl}-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acid (27.2 g) in tetrahydrofuran (75 ml) were added triethylamine (5.8 g) and chloroformic acid isobutyl ester (6.2 g), and the mixture was stirred for one hour. The precipitated salt was filtered, and the filtrate was added dropwise into a suspension of sodium borohydride (2.9 g) in tetrahydrofuran-ethanol (50 ml-50 ml) under ice-cooling. The mixture was stirred for one hour, and thereto 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 sodium chloride solution, and dried over sodium sulfate. The sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give 2-methyl-2-propanyl (3R)-3-[({4-[2-(dibenzylamino)ethyl]-2-(hydroxymethyl)-2,7-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl}carbonyl)(2-propanyl)amino]-1-piperidinecarboxylate (22.5 g).

Workup

  1. temperatureUnder nitrogen atmosphere, the mixture was cooled with ice-bath
  2. filtrationThe precipitated salt was filtered
  3. additionthe filtrate was added dropwise into a suspension of sodium borohydride (2.9 g) in tetrahydrofuran-ethanol (50 ml-50 ml) under ice-
  4. temperaturecooling
  5. stirringThe mixture was stirred for one hour
  6. additionwas added a saturated aqueous ammonium chloride solution
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  9. dry with materialdried over sodium sulfate
  10. customThe sodium sulfate was removed by filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ca8101e570754a089586a3bf8ffb9eee
Source dataset
uspto-grants-2014_02
Patent number
US08658639B2

Reaction notes

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