1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Benzyl 3-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)azetidine-1-carboxylate

HRID 415258Notes

Reaction equation

HRID 415258 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([C:15]([OH:17])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(N=C=NCCCN(C)C)C.[NH2:48][C:49]1[C:50]([OH:60])=[C:51]([CH:57]=[CH:58][CH:59]=1)[C:52]([O:54][CH2:55]C)=[O:53]>C.[Cl-].[Cl-].O>[OH:60][C:50]1[C:51]([C:52]([O:54][CH3:55])=[O:53])=[CH:57][CH:58]=[CH:59][C:49]=1[NH:48][C:15]([CH:13]1[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:14]1)=[O:17]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 109882141-[(Benzyloxy)carbonyl]azetidine-3-carboxylic acidHCID 22096614Ethyl 3-amino-2-hydroxybenzoate

Product 1

HCID 66621306Benzyl 3-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)azetidine-1-carboxylateYield 53.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 20976018Dichloride methaneSolvent

Procedure

To a solution of 1-(benzyloxycarbonyl)azetidine-3-carboxylic acid (2.4 g) in dichloride methane (15 ml) was added 1-hydroxybenzotriazole (1.48 mg, 11 mmol), diisopropylethylamine (4 g, 30 mmol) and 1-ethly-3-(3-dimethylaminopropyl)carbodiimide hydrochloric (2 g, 11 mmol). The mixture was stirred at room temperature for 30 min. Then ethyl 3-amino-2-hydroxybenzoate (700 mg, 4 mmol) was added. The mixture was stirred at room temperature for 2 h. To the resulting mixture, water (10 ml) was added and hydrochloride acid (1N) to pH=3, then extracted with ethyl acetate (100 ml×4). The organic phase was washed with sodium bicarbonate (saturated) and brine and concentrated, dried with sodium sulfate. The crude was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1). 820 mg of benzyl 3-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)azetidine-1-carboxylate was obtained. Yield 52%. LC-MS (ESI) m/z: 385 (M+1)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. extractionhydrochloride acid (1N) to pH=3, then extracted with ethyl acetate (100 ml×4)
  3. washThe organic phase was washed with sodium bicarbonate (saturated) and brine
  4. concentrationconcentrated
  5. dry with materialdried with sodium sulfate
  6. customThe crude was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1)

Sources & evidence

ORD record
ord-7d662d2c64e145bc9e915ef44005dc2e
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

Loading…