Diisopropylcarbodiimide → (2S)-Methyl-1-[(1,5-dimethylpyrazol-3-yl)carbonyl]azetidine-2-carboxylate

HRID 1264476Notes

Reaction equation

HRID 1264476 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[CH:5][C:4]([C:8]([OH:10])=O)=[N:3]1.C(N=C=NC(C)C)(C)C.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.CN(C1C=CC=CN=1)C.[NH:44]1[CH2:47][CH2:46][C@H:45]1[C:48]([O:50][CH3:51])=[O:49]>ClCCl>[CH3:51][O:50][C:48]([C@@H:45]1[CH2:46][CH2:47][N:44]1[C:8]([C:4]1[CH:5]=[C:6]([CH3:7])[N:2]([CH3:1])[N:3]=1)=[O:10])=[O:49]

Participants

7

Reactant 5

HCID 12734DiisopropylcarbodiimideHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 218852-DimethylaminopyridineHCID 5877571,5-dimethyl-1H-pyrazole-3-carboxylic acidHCID 13246223(S)-Methyl azetidine-2-carboxylate

Product 1

HCID 59049301(2S)-Methyl-1-[(1,5-dimethylpyrazol-3-yl)carbonyl]azetidine-2-carboxylateYield 58.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of the 1,5-dimethylpyrazole-3-carboxylic acid (433.1 mg, 3.09 mmol, 1.0 eq), diisopropylcarbodiimide (0.74 mL, 4.73 mmol, 1.5 eq), camphorsulfonic acid (300.6 mg, 1.29 mmol, 0.4 eq) and dimethylaminopyridine (129.7 mg, 1.06 mmol, 0.3 eq) in dry dichloromethane (30 mL) was added (2S)-methyl azetidine-2-carboxylate (474.4 mg, 3.13 mmol, 1.0 eq) in dry dichloromethane (12 mL) at about room temperature. The mixture was stirred at about room temperature for about 24 hours under argon. The solid was filtered off and washed with ether. The organic filtrate was concentrated and the residue subjected to flash chromatography (1-10% methanol in dichloromethane) to give 429.9 mg (58% yield) of the product. 1H NMR (CDCl3) δ 2.22-2.77 (series of s and m, 5H); 3.64-3.84 (series of s, 6H); 4.08-4.73 (series of m, 2H); 4.89 and 5.29 (dd, 1H, J=9.4, 6.0); 6.53 (s, 1H).

Workup

  1. filtrationThe solid was filtered off
  2. washwashed with ether
  3. concentrationThe organic filtrate was concentrated

Sources & evidence

ORD record
ord-41825587b05a44d6828a76245dbf26fa
Source dataset
uspto-grants-2003_04
Patent number
US06544976B1

Reaction notes

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