Cyclopropanecarbonyl chloride → Methyl 2-chloro-5-(cyclopropanecarboxamidomethyl)benzoate

HRID 59326Notes

Reaction equation

HRID 59326 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[CH:5][C:6]([Cl:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9].CCN(C(C)C)C(C)C.[CH:23]1([C:26](Cl)=[O:27])[CH2:25][CH2:24]1>C1COCC1>[Cl:13][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:1][C:26]([CH:23]2[CH2:25][CH2:24]2)=[O:27])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 66524841Methyl 5-(aminomethyl)-2-chlorobenzoate

Product 1

HCID 89443034Methyl 2-chloro-5-(cyclopropanecarboxamidomethyl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 5-(aminomethyl)-2-chlorobenzoate (15.0 g, 75 mmol) in dry THF (150 mL) was added DIPEA (15 mL) under nitrogen atmosphere. Cyclopropanecarbonyl chloride was added to the reaction mixture at 10° C. and (11.81 g, 113 mmol). The reaction mixture was stirred at RT for 5-6 h. The reaction mixture was quenched with ice water and extracted with ethyl acetate. The organic layer was washed with dilute HCl, followed with sodium bicarbonate solution and concentrated to afford 10.0 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 0.69 (m, 4H), 1.59 (m, 1H), 3.86 (s, 3H), 4.29 (d, J=6.0 Hz, 2H), 7.43 (d, J=6.6 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.67 (s, 1H), 8.64 (br s, 1H); MS (m/z): 268.16 (M+H)+.

Workup

  1. customThe reaction mixture was quenched with ice water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with dilute HCl
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a60cd1d3a9874fa787e00ca79b1cef7a
Source dataset
uspto-grants-2016_09
Patent number
US09439890B2

Reaction notes

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