Potassium Carbonate → 2-(4-Amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

HRID 385351Notes

Reaction equation

HRID 385351 reaction equation
[CH:1]1([CH2:4][O:5][C:6](=[O:24])[CH:7]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([O:19][CH2:20][CH:21]3[CH2:23][CH2:22]3)[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1.[Cl:25]N1C(=O)CCC1=O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl>[CH:1]1([CH2:4][O:5][C:6](=[O:24])[CH:7]([C:12]2[CH:13]=[C:14]([O:19][CH2:20][CH:21]3[CH2:23][CH2:22]3)[C:15]([NH2:18])=[C:16]([Cl:25])[CH:17]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 31398ChlorosuccinimideHCID 579955632-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

Product 1

HCID 579955842-(4-Amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl esterYield 36%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

2-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (16.3 g, 49.1 mmol) was dissolved in chloroform (200 mL) and N-chlorosuccinimide (5.3 g, 0.75 equiv, 39.6 mmol) was added. The reaction mixture was refluxed for 1 h and after cooling treated with 10% potassium carbonate solution (100 mL). The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were dried over magnesium sulfate. Evaporation of the solvent gave the crude product as a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give 2-(4-amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (5 g, 36%). 1H NMR (300 MHz, CDCl3/TMS): δ 6.85 (s, 1H), 6.66 (s, 1H), 3.95-3.80 (m, 4H), 3.49 (t, J=7.7 Hz, 1H), 1.94-1.82 (m, 1H), 1.63-1.52 (m, 1H), 1.50-1.40 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.66-0.58 (m, 2H), 0.53-0.47 (m, 2H), 0.37-0.32 (m, 2H), 0.25-0.20 (m, 2H); 13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 146.8, 132.6, 128.7, 120.6, 118.3, 109.4, 73.6, 69.3, 49.0, 42.6, 25.9, 22.6, 22.4, 10.4, 9.8, 3.3.

Workup

  1. temperatureThe reaction mixture was refluxed for 1 h
  2. temperatureafter cooling
  3. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
  4. dry with materialthe combined organic phases were dried over magnesium sulfate
  5. customEvaporation of the solvent
  6. customgave the crude product as a brown oil, which
  7. customwas purified by silica gel gradient column chromatography by use of Heptane-EtOAc

Sources & evidence

ORD record
ord-5b01e3c46b9b46aba97741b9dd5a174e
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

Loading…