Methanol → HCID 58797588, compound

HRID 1593020Notes

Reaction equation

HRID 1593020 reaction equation
[N:1]1[NH:2][N:3]=[N:4][C:5]=1[CH:6]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1.[C:19]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.CO>C1COCC1>[CH3:19][N:2]1[N:3]=[N:4][C:5]([CH:6]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)=[N:1]1

Participants

6

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 18187701Tert-butyl 4-(2H-tetrazol-5-YL)piperidine-1-carboxylate

Product 1

HCID 58797588HCID 58797588, compoundYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(2H-tetrazol-5-yl)piperidine-1-carboxylate (CAS 91419-58-8) (0.98 g, 3.89 mmol) and triphenylphosphine (3.06 g) in THF under a blanket of Ar was added the diisopropyl azodicarboxylate (2.30 ml) and the mixture stirred for 10 minutes. Methanol (473 μl) was added and the reaction was stirred for 18 hours and then the solution was concentrated in vacuo. The residue was purified on silica using a 90 g Biotage cartridge and a gradient elution of 25 to 35% ethyl acetate in hexanes. This semi-pure mixture was partially dissolved in a 4M HCl in dioxane solution and stirred for 1 hour, then concentrated in vacuo. The residue was partially dissolved in DCM (40 ml) and triethylamine (162 μl) and MP-Carbonate (4.17 g, loading 2.8 mmol/g) added and slurry stirred for 64 hours. The resin was filtered off and washed with a 10% solution of methanol in DCM and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on SCX-2 stationary phase using methanol and then a 1M ammonia in methanol solution. Evaporation of the solvent under reduced pressure gave the title compound as a yellow solid (0.502 g); NMR (CDCl3): 1.78 (2H, m), 2.06 (2H, d), 2.77 (2H, m), 3.08 (1H, m), 3.19 (2H, d), 3.08 (3H, s).

Workup

  1. stirringthe reaction was stirred for 18 hours
  2. concentrationthe solution was concentrated in vacuo
  3. customThe residue was purified on silica using a 90 g Biotage cartridge
  4. washa gradient elution of 25 to 35% ethyl acetate in hexanes
  5. dissolutionThis semi-pure mixture was partially dissolved in a 4M HCl in dioxane solution
  6. stirringstirred for 1 hour
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was partially dissolved in DCM (40 ml)
  9. additiontriethylamine (162 μl) and MP-Carbonate (4.17 g, loading 2.8 mmol/g) added
  10. stirringslurry stirred for 64 hours
  11. filtrationThe resin was filtered off
  12. washwashed with a 10% solution of methanol in DCM
  13. concentrationthe filtrate was concentrated in vacuo
  14. customThe residue was purified by column chromatography on SCX-2 stationary phase
  15. customEvaporation of the solvent under reduced pressure

Sources & evidence

ORD record
ord-d4490e2da7f04a29920183716bfeaf89
Source dataset
uspto-grants-2007_11
Patent number
US07294636B2

Reaction notes

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