Pyridine → HCID 66620870, compound

HRID 415333Notes

Reaction equation

HRID 415333 reaction equation
[NH2:1][C:2]1[C:3]([OH:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.Cl[C:20]([C:22]1[CH:41]=[CH:40][C:25]([CH2:26][CH2:27][N:28]([CH3:39])[C:29](=[O:38])[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:24][CH:23]=1)=[O:21]>C1(C)C=CC=CC=1>[CH2:31]([O:30][C:29]([N:28]([CH3:39])[CH2:27][CH2:26][C:25]1[CH:24]=[CH:23][C:22]([C:20]([NH:1][C:2]2[C:3]([OH:12])=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[O:21])=[CH:41][CH:40]=1)=[O:38])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 12782444Methyl 3-amino-2-hydroxybenzoateHCID 86633100HCID 86633100, compound

Product 1

HCID 66620870HCID 66620870, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

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. wait80° C. for 1 h
  3. washwashed with water (30 mL×3), 1N hydrochloric acid (30 mL×3), brine (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography ((silica gel, petroleum ether/ethyl acetate 15:1 to 4:1)

Sources & evidence

ORD record
ord-9042f49e8cee427ab4b2add501255c4d
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

Loading…