Dichloromethane → HCID 67135214, compound

HRID 1694298Notes

Reaction equation

HRID 1694298 reaction equation
Br.Br.CN1CC2CC1CN2.[CH3:11][N:12]1[CH2:17][CH:16]2[CH2:18][CH:13]1[CH2:14][N:15]2[CH:19]1[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]1.O=C1CCN(C(OC(C)(C)C)=O)CC1.C(N(CC)CC)C.[Cl:53]CCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[ClH:53].[ClH:53].[CH3:11][N:12]1[CH2:17][CH:16]2[CH2:18][CH:13]1[CH2:14][N:15]2[CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1

Participants

8

Reactant 6

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 86645407HCID 86645407, compound

Product 1

HCID 67135214HCID 67135214, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidine-1-carboxylate 2-Methyl-2,5-diazabicyclo[2.2.1]heptane dihydrobromide (1.715 mmol, 1 eq.), tert-butyl 4-oxopiperidine-1-carboxylate (2.401 mmol, 1.4 eq.) and triethylamine (4.288 mmol, 2.5 eq.) were dissolved in dichloromethane (120 mmol, 70 eq.) and the resulting mixture was stirred for 5 min at RT under nitrogen. Subsequently sodium triacetoxy borohydride (2.401 mmol, 1.4 eq.) was added and the mixture stirred for 16 h at RT. Ethyl acetate (30 ml) and sat. aq. sodium hydrogen carbonate solution (30 ml) were added to the reaction mixture and it was stirred for 15 min. The phases were separated and the aqueous phase was extracted with ethyl acetate (3×30 ml). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography (ethyl acetate/methanol/DCM, 10:10:5+25% aq ammonia) to yield the title compound. Yield: 0.35 g (69%) 2. 2-Methyl-5-(piperidin-4-yl)-2,5-diazabicyclo[2.2.1]heptane dihydrochloride Tert-butyl 4-(5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)piperidine-1-carboxylate (1.158 mmol, 1 eq.) was dissolved in Ethanol (7 ml) and acetyl chloride (5.76 mmol, 5 eq.) was added at 0° C. The mixture was stirred at RT for 16 h, at which time a light solid had precipitated. The suspension was diluted with diethyl ether (30 ml) and the solid was collected by filtration and washed with diethyl ether (50 ml). The title compound thus obtained was dried under high vacuum. Yield: 0.34 g (>99%)

Workup

  1. stirringthe mixture stirred for 16 h at RT
  2. stirringwas stirred for 15 min
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (3×30 ml)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (ethyl acetate/methanol/DCM, 10:10:5+25% aq ammonia)

Sources & evidence

ORD record
ord-c0329e6346ea4ae8a08b39b298159042
Source dataset
uspto-grants-2012_04
Patent number
US08158628B2

Reaction notes

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