4-Methylmorpholine → HCID 58355418, compound

HRID 1509570Notes

Reaction equation

HRID 1509570 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:22]=[N:23][N:24]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[CH3:38])[C:25]=2[CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:39](O)=[O:40])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC.[BH4-].[Na+]>C1COCC1.C(=O)([O-])O.[Na+].CO>[OH:40][CH2:39][C@@H:10]1[CH2:11][C@H:12]([N:14]([C:19]([C:21]2[N:22]=[N:23][N:24]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[CH3:38])[C:25]=2[CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:13][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:9]1

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 58355662HCID 58355662, compound

Product 1

HCID 58355418HCID 58355418, compoundYield 80.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

(3R,5S)-1-(tert-Butoxycarbonyl)-5-[({5-[(2-methoxyethoxy)methyl]-1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl}carbonyl)(2-methylpropyl)amino]piperidine-3-carboxylic acid (900 mg) and 1-methylmorpholine (274 μl) were dissolved in THF (5 ml), ethyl chlorocarbonate (230 μl) was added under ice-cooling and the mixture was stirred at 0° C. for 1 hr. Sodium tetrahydroborate (200 mg) and methanol (2 ml) were added to the reaction mixture, and the mixture was further stirred at room temperature for 14 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (10:90-90:10) was concentrated under reduced pressure to give the object product (704 mg).

Workup

  1. temperaturecooling
  2. stirringthe mixture was further stirred at room temperature for 14 hr
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. washa fraction eluted with ethyl acetate-hexane (10:90-90:10)
  8. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-99b0bef1b379475aa17f544f2cea314b
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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