Dichloromethane → benzyl 3-(1H-tetrazol-5-yl)pyrrolidine-1-carboxylate

HRID 1454349Notes

Reaction equation

HRID 1454349 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([C:16]#[N:17])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:18]=[N+:19]=[N-:20].[Na+].[Cl-].[NH4+].C(Cl)Cl>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH:13]([C:16]2[NH:20][N:19]=[N:18][N:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 19067843Benzyl 3-cyanopyrrolidine-1-carboxylate

Product 1

HCID 178525125benzyl 3-(1H-tetrazol-5-yl)pyrrolidine-1-carboxylateYield 31.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 1.8 g (7.8 mmol) of (R/S)-1-benzyloxycarbonyl-3-cyano pyrrolidine (from Step A), 1.5 g (23 mmol) of sodium azide and 1.25 g (23 mmol) of ammonium chloride in 70 mL of DMF was stirred at 105° C. overnight. After cooling to rt, the reaction was poured into 150 mL of CH2Cl2 and washed with 150 mL of 1N HCl and 2×150 mL of H2O. The organic phase was dried over MgSO4 and concentrated. The residue was purified on a 40M Biotage column using 80:20:1 v/v/v CH2Cl2/EtOAc/HOAc as the eluant to afford 670 mg (31%) of the title compound: RF: 0.23 (80:20:1 v/v/v CH2Cl2/EtOAc/HOAc); 1H-NMR (500 MHz) δ 2.29, 2.48 (2m, 2H), 3.54-4.03 (m, 5H), 5.14-5.24 (m, 2H), 7.30-7.37 (m, 5H), 10.43 (br, 1H).

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with 150 mL of 1N HCl and 2×150 mL of H2O
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified on a 40M Biotage column

Sources & evidence

ORD record
ord-25a82772274f428886df0f91a84ba1ff
Source dataset
uspto-grants-2009_01
Patent number
US07479504B2

Reaction notes

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