Pyrrolidine → 1-Azetidinecarboxylic acid, 3-(1-pyrrolidinylcarbonyl)-, 1,1-dimethylethyl ester

HRID 1922684Notes

Reaction equation

HRID 1922684 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:6]([O:10][C:11]([N:13]1[CH2:16][CH:15]([C:17](O)=[O:18])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:6]([O:10][C:11]([N:13]1[CH2:16][CH:15]([C:17]([N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:18])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 674920351-Azetidinecarboxylic acid, 3-(1-pyrrolidinylcarbonyl)-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Pyrrolidine (271 μL, 5.50 mmol) was added to a solution of azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (1.0 g, 4.97 mmol), HATU (2.09 g, 5.50 mmol) and DIPEA (2.18 mL, 12.52 mmol) in DMF (100 mL) and the resulting mixture stirred at ambient temperature for 1 h, then concentrated in vacuo. The resulting oil was partitioned between EtOAc and water. The organic layer was separated, washed with water and brine, then dried (MgSO4) and concentrated in vacuo to give 3-(pyrrolidine-1-carbonyl)azetidine-1-carboxylic acid tert-butyl ester as a colourless oil. TFA (3 mL) was added to a solution of 3-(pyrrolidine-1-carbonyl)-azetidine-1-carboxylic acid tert-butyl ester in DCM (15 mL) and the mixture stirred at ambient temperature for 1 h, then loaded onto an Isolute® SCX-2 cartridge (25 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo to afford the title compound as a colourless oil (550 mg, 72%). 1H NMR (CD3OD, 400 MHz) δ 3.93-3.65 (m, 5H); 3.43-3.28 (m, 4H) and 2.00-1.81 (m, 4H).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe resulting oil was partitioned between EtOAc and water
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c9a19c0e300e4c26a432da089809f1fc
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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