Phosphorus tribromide → Ethyl 3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate

HRID 14022

Reaction equation

HRID 14022 reaction equation
[CH2:1]([N:4]([CH2:20][CH2:21][CH3:22])[C:5]([C:7]1[CH:8]=[C:9]([CH:15]=[C:16]([CH2:18]O)[CH:17]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:6])[CH2:2][CH3:3].P(Br)(Br)[Br:24]>ClCCl>[Br:24][CH2:18][C:16]1[CH:15]=[C:9]([CH:8]=[C:7]([C:5]([N:4]([CH2:20][CH2:21][CH3:22])[CH2:1][CH2:2][CH3:3])=[O:6])[CH:17]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

4

Reactant 2

HCID 24614Phosphorus tribromideHCID 21086103Ethyl 3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoate

Product 1

HCID 21086099Ethyl 3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl 3-[(dipropylamino)carbonyl]-5-(hydroxymethyl)benzoate (1.5 g) and phosphorous tribromide (0.95 mL) is stirred in dichloromethane (10 mL) and heated at 50 degrees C. for 4 hours and then cooled and partitioned between dichloromethane and water. The organic phase is separated and washed with aqueous sodium bicarbonate and then dried over magnesium sulfate and taken to dryness to give ethyl 3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate, high resolution MS MH+=370.1020. Ethyl 3-(bromomethyl)-5-[(dipropylamino)carbonyl]benzoate (1.4 g) and sodium cyanide (0.2 g) are stirred in dry DMSO (25 mL) at 20-25 degrees C. for 3.5 hours and the mixture is then partitioned between ethyl acetate, water and saline. The organic layer is separated and dried over magnesium sulfate and taken to dryness under reduced pressure to give ethyl 3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoate. Ethyl 3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoate (0.6 g) is hydrolyzed with lithium hydroxide monohydrate (0.1 g) in ethanol and water at 20-25 degrees C. overnight and then added to water (50 mL). The pH is adjusted to 4 using concentrated hydrochloric acid and the mixture is partitioned between ethyl acetate, water, and saline. The organic phase is separated and dried over magnesium sulfate and taken to dryness under reduced pressure to give 3-(cyanomethyl)-5-[(dipropylamino)carbonyl]benzoic acid, MS M+H=287.2.

Workup

  1. temperaturecooled
  2. custompartitioned between dichloromethane and water
  3. customThe organic phase is separated
  4. washwashed with aqueous sodium bicarbonate
  5. dry with materialdried over magnesium sulfate

Sources & evidence

ORD record
ord-515a8a44044e44bd9256e0d3953e263c
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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