Azetidine → tert-Butyl 4-(azetidin-1-yl)piperidine-1-carboxylate

HRID 1365869Notes

Reaction equation

HRID 1365869 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:15]1[CH2:18][CH2:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:15]2[CH2:18][CH2:17][CH2:16]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10422AzetidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 59418226tert-Butyl 4-(azetidin-1-yl)piperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (1.75 g, 8.88 mmol) in dichloroethane (80 mL) was added azetidine (0.6 g, 10.53 mmol) and the mixture was stirred at RT for 30 min. Sodium triacetoxyborohydride (3.9 g, 18.44 mmol) was added and the resulting solution was stirred at RT for 18 h. The reaction mixture was partitioned between water and DCM and the layers separated. The organic layer was extracted further with DCM and the combined aqueous layers were concentrated in vacuo. The resultant white semi-solid was suspended in DCM and a saturated aqueous solution of NaHCO3 was added. The layers were thoroughly mixed, the organic layer isolated and the aqueous layer further extracted with DCM. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo to give 4-azetidin-1-yl-piperidine-1-carboxylic acid tert-butyl ester as a white solid (2.0 g, 95%). BOC-deprotection of 4-azetidin-1-yl-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 1.67 mmol) using TFA:DCM (1:4) gave the title compound as a yellow oil (185 mg, 79%)

Workup

  1. stirringthe resulting solution was stirred at RT for 18 h
  2. customThe reaction mixture was partitioned between water and DCM
  3. customthe layers separated
  4. extractionThe organic layer was extracted further with DCM
  5. concentrationthe combined aqueous layers were concentrated in vacuo
  6. additiona saturated aqueous solution of NaHCO3 was added
  7. additionThe layers were thoroughly mixed
  8. customthe organic layer isolated
  9. extractionthe aqueous layer further extracted with DCM
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0e79b14db954dab933554bbb992334f
Source dataset
uspto-grants-2011_02
Patent number
US07893060B2

Reaction notes

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