3-{[(2,4-Dichlorobenzyl)-(3-oxo-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl ester → 3-{[(2,4-Dichlorobenzyl)-(3-hydroxy-3-methyl-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl ester

HRID 1435155Notes

Reaction equation

HRID 1435155 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][N:13]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])[CH2:14][CH2:15][C:16](=[O:18])[CH3:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:28][Mg+].[Br-]>CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][N:13]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[Cl:27])[CH2:14][CH2:15][C:16]([OH:18])([CH3:28])[CH3:17])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 690048573-{[(2,4-Dichlorobenzyl)-(3-oxo-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl esterHCID 178418689HCID 178418689, compound

Product 1

HCID 690038323-{[(2,4-Dichlorobenzyl)-(3-hydroxy-3-methyl-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 3-{[(2,4-dichlorobenzyl)-(3-oxo-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl ester (190 mg, 0.46 mmol) in Et2O (4 mL) is added MeMgBr (3.0 M in Et2O, 0.92 mmol). The resulting mixture is stirred at room temperature for one hour. The reaction is quenched with saturated ammonium chloride and extracted with EtOAc (3×). The combined organic extracts are dried (Na2SO4), filtered and concentrated. The crude product is purified by flash chromatography on silica gel eluting with 5% EtOH (10% NH4OH)/chloroform to yield 138 mg (70%) of 3-{[(2,4-dichlorobenzyl)-(3-hydroxy-3-methyl-butyl)-amino]-methyl}-azetidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CD3OD) δH: 7.49-7.47 (2H, m), 7.36-7.34 (1H, m), 4.0-3.96 (2H, m), 3.67 (2H, s), 3.57-3.53 (2H, m), 2.9-2.82 (1H, m), 2.75-2.73 (2H, m), 2.67 (2H, t, J=7.0 Hz), 1.69 (2H, t, J=7.3 Hz), 1.46 (9H, s), 1.1 (6H, s). Mass spectrum (ion spray): m/z=431.2 (M+H).

Workup

  1. customThe reaction is quenched with saturated ammonium chloride
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic extracts are dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product is purified by flash chromatography on silica gel eluting with 5% EtOH (10% NH4OH)/chloroform

Sources & evidence

ORD record
ord-5b0ab043a3a54ec79fa09c5bdca6b825
Source dataset
uspto-grants-2009_11
Patent number
US07615648B2

Reaction notes

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