Thionyl Chloride → HCID 86633100, compound

HRID 415332Notes

Reaction equation

HRID 415332 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH3:23])[CH2:12][CH2:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:26])=O>ClCCl>[Cl:26][C:18]([C:17]1[CH:21]=[CH:22][C:14]([CH2:13][CH2:12][N:11]([CH3:23])[C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:15][CH:16]=1)=[O:19]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 66621435HCID 66621435, compound

Product 1

HCID 86633100HCID 86633100, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(2-((benzyloxycarbonyl)(methyl)amino)ethyl)benzoic acid (2.0 g, 6.38 mmol) in anhydrous dichloromethane (30 mL) was added dropwise thionyl chloride (1.52 g, 12.76 mmol) at 0° C. After the addition, the solution was stirred at room temperature overnight. Solvent was removed in vacuum to give benzyl 4-(chlorocarbonyl)phenethyl(methyl)carbamate. To a stirred solution of methyl 3-amino-2-hydroxybenzoate (0.71 g, 4.25 mmol) and pyridine (0.19 mL, 10.2 mmol) in anhydrous toluene (20 mL) was added dropwise a solution of benzyl 4-(chlorocarbonyl)phenethyl(methyl)carbamate (1.7 g, 5.1 mmol) in anhydrous toluene (5 mL). After the addition, the mixture was stirred at room temperature 30 min, then 80° C. for 1 h. The mixture was diluted with toluene, washed with water (30 mL×3), 1N hydrochloric acid (30 mL×3), brine (30 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography ((silica gel, petroleum ether/ethyl acetate 15:1 to 4:1), to obtain methyl 3-(4-(2-((benzyloxycarbonyl)(methyl)amino)ethyl)benzamido)-2-hydroxybenzoate (1.9 g, yield 97%) as yellow oil. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 2.82-2.87 (m, 5H), 3.49-3.53 (t, J=7 Hz, 2H), 3.94 (s, 1H), 4.98-5.06 (d, J=32 Hz, 2H), 6.98-7.02 (t, J=8 Hz, 1H), 7.26-7.39 (m, 7H), 7.66-7.68 (d, J=7.6 Hz, 1H), 7.89-7.91 (m, 2H), 7.94-7.96 (d, J=8 Hz, 1H), 9.61 (s, 1H), 10.92 (s, 1H); LC-MS (ESI) m/z: 463 (M+1)+.

Workup

  1. additionAfter the addition
  2. customSolvent was removed in vacuum

Sources & evidence

ORD record
ord-6932931ac77346c3b870a775dcd356c5
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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