3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → Tert-butyl 3-(3-hydroxy-3-methyl-azetidin-1-YL)azetidine-1-carboxylate

HRID 1922702Notes

Reaction equation

HRID 1922702 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:13][C:14]1([OH:18])[CH2:17][NH:16][CH2:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:16]2[CH2:17][C:14]([OH:18])([CH3:13])[CH2:15]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 115427823-Methylazetidin-3-ol

Product 1

HCID 59605621Tert-butyl 3-(3-hydroxy-3-methyl-azetidin-1-YL)azetidine-1-carboxylateYield 30.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A 10 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (0.21 g, 1.23 mmol), 3-methylazetidin-3-ol (0.13 g, 1.48 mmol) and 4 Å molecular sieves (1.2 g) in DCE (5 mL). The reaction mixture was stirred for 3 h at room temperature. Sodium triacetoxyborohydride (0.52 g, 2.47 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the solution was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, 0:100 to 100:0) to give 3-Hydroxy-3-methyl-[1,3′]biazetidinyl-1′-carboxylic acid tert-butyl ester as a colourless oil (0.09 g, 30%). 1H NMR (300 MHz, CDCl3): δ 3.93 (dd, J=9.2, 7.2 Hz, 2H), 3.82-3.70 (m, 2H), 3.50-3.40 (m, 1H), 3.32 (d, J=8.1 Hz, 2H), 3.21 (d, J=8.1 Hz, 2H), 1.51 (s, 3H), 1.43 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe solution was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, 0:100 to 100:0)

Sources & evidence

ORD record
ord-68d45468bcc649de91f5164831a4486d
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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