Methylamine → HCID 25104294, compound

HRID 906677Notes

Reaction equation

HRID 906677 reaction equation
[CH3:1][NH2:2].Cl.CN.[OH-].[Na+].[C:8]([N:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1)([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[N:22]1[O:23][N:24]=[C:25]2[CH:30]=[C:29]([C:31](Cl)=[O:32])[CH:28]=[CH:27][C:26]=12>CO.C1COCC1.CCN(CC)CC.ClCCl.[Pd]>[C:11]([O:10][C:8]([N:15]1[CH2:20][CH2:19][CH:18]([N:2]([C:31]([C:29]2[CH:28]=[CH:27][C:26]3=[N:22][O:23][N:24]=[C:25]3[CH:30]=2)=[O:32])[CH3:1])[CH2:17][CH2:16]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

11

Reactant 5

HCID 6329MethylamineHCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27354532,1,3-Benzoxadiazole-5-carbonyl chlorideHCID 6364545Methylamine hydrochloride

Product 1

HCID 25104294HCID 25104294, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Methylamine (generated by heating a mixture of 10 g of methylamine hydrochloride and 18 g of sodium hydroxide) was condensed into a solution of Boc-4-piperidone (3.5 g, 17.6 mmol) in methanol (30 ml) and THF (30 ml). 10% Pd on C (600 mg) was added and the mixture was hydrogenated at room temperature for 18 hours. The solids were filtered off, washed with methanol (20 ml) and concentrated under vacuum. The residue was dissolved in chloroform (50 ml) and NEt3 (4 ml), and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (2.1 g, 11.5 mmol) in dichloromethane (20 ml) was added slowly. After stirring the mixture for 1 h, the organic phase was washed with water (100 ml) and H2SO4 (→pH 2) and NaHCO3 solution (100 ml). The aqueous was extracted with chloroform (100 ml), the organics combined, dried (MgSO4) and concentrated under vacuum to give an oil. The crude product was purified by silica gel chromatography eluting with ethyl acetate/hexane (40:60) →(60:40) to give a white solid after crystallization from MTBE/hexane (3.14 g). Mp=98-100° C., LC-MS, MH+=361; 1H NMR (300 MHz, CDCl3) δ 7.93 (d, J=9.0 Hz, 1H); 7.84 (s, 1H); 7.42 (d, J=9.0 Hz, 1H); 4.80-3.40 (m, 5H); 3.10-2.85 (m, 3H); 1.90-1.60 (m, 4H); 1.47 ppm (s, 9H).

Workup

  1. temperatureby heating
  2. filtrationThe solids were filtered off
  3. washwashed with methanol (20 ml)
  4. concentrationconcentrated under vacuum
  5. dissolutionThe residue was dissolved in chloroform (50 ml)
  6. washthe organic phase was washed with water (100 ml) and H2SO4 (→pH 2) and NaHCO3 solution (100 ml)
  7. extractionThe aqueous was extracted with chloroform (100 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under vacuum
  10. customto give an oil
  11. customThe crude product was purified by silica gel chromatography
  12. washeluting with ethyl acetate/hexane (40:60) →(60:40)
  13. customto give a white solid
  14. customafter crystallization from MTBE/hexane (3.14 g)

Sources & evidence

ORD record
ord-483cb5b3ae8c41819eb710544b8fbd36
Source dataset
uspto-grants-2011_09
Patent number
US08013003B2

Reaction notes

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