Water → HCID 21219160, compound

HRID 1585647Notes

Reaction equation

HRID 1585647 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(N(C(C)C)C(C)C)C.O>C(OCC)C.CO.Cl>[CH2:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:16]=[N:15]2)[CH2:12][CH2:13]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 81531DiisopropylethylamineHCID 121609091,1-Dimethylethyl 4-(4-phenyl-1H-1,2,3-triazol-1-yl)-1-piperidinecarboxylate

Product 1

HCID 21219160HCID 21219160, compoundYield 7.9%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolvent4×HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of N-t butyloxycarbonyl-4-((4-phenyl)triazol-1-yl)piperidine (2.5 g) in a 1:1 mixture of diethyl ether and methanol (10 ml) was added a solution of hydrogen chloride in methanol (10 ml, ~5 mol) and the reaction mixture was stirred at room temperature for 72 hrs. The solid was filtered off and dried then redissolved in N,N-dimethylformamide (20 ml), to which was added benzyl bromide (0.4 ml, 3.4 mmol) and ethyldiisopropylamine (0.55 ml, 3.4 mmol). The reaction mixture was stirred at room temperature for 18 hrs under nitrogen, then poured into water (200 ml) and extracted with dichloromethane (3×100 ml). The combined organic layers were washed with brine (2×50 ml), dried (MgSO4), filtered and concentrated under vacuum. The residue was purified by flash silica chromatography using methanol in dichloromethane (0-4%) and ammonia (0.5%). The product obtained was redissolved in a 1:1 mixture of diethyl ether and methanol (5 ml) with hydrogen chloride in methanol (10 ml, ~5 mol). After 5 mins the solvent was removed under vacuum and the residue was recrystallized from methanol and ethyl acetate to give the required product as a white solid (85 mg). M.p 206-280° C. 1H NMR (DMSO) δ 2.11 (4H,m), 2.60 (2H,m), 2.77 (2H,m), 3.04 (2H,m), 4.52 (1H,m), 7.18-7.85 (11H,m). MS (CI) m/e 319 [MH]+. Anal. Found C, 64.90; H, 6.43; N, 15.05. C20H22N4.HCl.0.75H2O requires C, 65.21; H, 6.70; N, 15.21%.

Workup

  1. filtrationThe solid was filtered off
  2. customdried
  3. dissolutionthen redissolved in N,N-dimethylformamide (20 ml), to which
  4. stirringThe reaction mixture was stirred at room temperature for 18 hrs under nitrogen
  5. extractionextracted with dichloromethane (3×100 ml)
  6. washThe combined organic layers were washed with brine (2×50 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by flash silica chromatography
  11. customThe product obtained
  12. customAfter 5 mins the solvent was removed under vacuum
  13. customthe residue was recrystallized from methanol and ethyl acetate

Sources & evidence

ORD record
ord-20ca0d28f5e74691b1793b0a0346d868
Source dataset
uspto-grants-1999_08
Patent number
US05939436

Reaction notes

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