Sodium Hydroxide → tert-butyl (3S,5R)-3-{[(2-tert-butyl-4-hexylpyrimidin-5-yl)carbonyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1509544Notes

Reaction equation

HRID 1509544 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:8]([C:17]([N:19]([CH2:37][CH:38]([CH3:40])[CH3:39])[C@@H:20]2[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23][C@H:22]([C:33](OC)=[O:34])[CH2:21]2)=[O:18])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-:41].[Na+]>CO.C1COCC1>[C:1]([C:5]1[N:10]=[C:9]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:8]([C:17]([N:19]([CH2:37][CH:38]([CH3:39])[CH3:40])[C@H:20]2[CH2:21][C@@H:22]([C:33]([N:6]3[CH2:7][CH2:8][O:41][CH2:1][CH2:5]3)=[O:34])[CH2:23][N:24]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[CH2:25]2)=[O:18])=[CH:7][N:6]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 583555751-tert-Butyl 3-methyl(3R,5S)-5-{[(2-tert-butyl-4-hexylpyrimidin-5-yl)carbonyl](2-methylpropyl)amino}piperidine-1,3-dicarboxylate

Product 1

HCID 58355247tert-butyl (3S,5R)-3-{[(2-tert-butyl-4-hexylpyrimidin-5-yl)carbonyl](2-methylpropyl)amino}-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-tert-Butyl 3-methyl (3R,5S)-5-{[(2-tert-butyl-4-hexylpyrimidin-5-yl)carbonyl](2-methylpropyl)amino}piperidine-1,3-dicarboxylate (219 mg) was dissolved in methanol (3 ml) and THF (2 ml), 1M aqueous sodium hydroxide solution (2 ml) was added and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the aqueous layer of the mixture was adjusted to pH 5-6 with saturated aqueous ammonium chloride solution, and the mixture was 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 obtained residue, morpholine (41 μl), 1H-benzotriazol-1-ol (30 mg) and triethylamine (140 μl) were dissolved in 1,2-dichloroethane (4 ml), WSC.HCl (115 mg) was added and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into water, and the mixture was 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 (5:95-80:20) was concentrated under reduced pressure to give the object product (88 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionThe obtained residue, morpholine (41 μl), 1H-benzotriazol-1-ol (30 mg) and triethylamine (140 μl) were dissolved in 1,2-dichloroethane (4 ml)
  7. additionWSC.HCl (115 mg) was added
  8. stirringthe mixture was stirred at room temperature for 3 days
  9. additionThe reaction mixture was poured into water
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. washa fraction eluted with ethyl acetate-hexane (5:95-80:20)
  15. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-d7b0f27ee10e427797c5c8b36deffc66
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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