Potassium Hydroxide → 2-(4-Benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid

HRID 385353Notes

Reaction equation

HRID 385353 reaction equation
C1(C[O:5][C:6](=[O:33])[CH:7]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)[C:15]([C:23]3[CH:24]=[CH:25][C:26]4[C:27]([CH:31]=3)=[N:28][O:29][N:30]=4)=[C:14]([Cl:32])[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])CC1.[OH-].[K+]>CCO.O>[N:30]1[O:29][N:28]=[C:27]2[CH:31]=[C:23]([C:15]3[C:16]([O:18][CH2:19][CH:20]4[CH2:22][CH2:21]4)=[CH:17][C:12]([CH:7]([CH2:8][CH:9]([CH3:10])[CH3:11])[C:6]([OH:33])=[O:5])=[CH:13][C:14]=3[Cl:32])[CH:24]=[CH:25][C:26]=12

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 579956022-(4-Benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester

Product 1

HCID 579956502-(4-Benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acidYield 71.3%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

2-(4-Benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.11 g, 0.23 mmol) was dissolved in a mixture of EtOH/H2O (9 mL/1 mL) and KOH (0.1 g, 1.76 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5, and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give 2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid as a yellow oil (0.068 g, 70%). 1H NMR (300 MHz, CDCl3/TMS): δ 8.40 (br s, 1H), 7.70 (d, J=9.3 Hz, 1H), 7.62 (s, 1H), 7.19 (d, J=9.3 Hz, 1H), 6.97 (s, 1H), 6.73 (s, 1H), 3.67 (d, J=6.6 Hz, 2H), 3.52 (t, J=7.7 Hz, 1H), 1.90-1.81 (m, 1H), 1.62-1.53 (m, 1H), 1.50-1.39 (m, 1H), 0.98-0.68 (m, 1H), 0.81 (d, J=6.1 Hz, 6H), 0.37-0.31 (m, 2H), 0.15-0.10 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 179.1, 157.1, 149.1, 148.3, 141.0, 138.6, 135.3, 133.7, 126.8, 121.6, 117.4, 115.0, 110.9, 73.4, 49.4, 41.9, 25.9, 22.6, 22.3, 10.0, 3.1.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was refluxed for 2 h
  3. temperatureafter cooling the solvent
  4. customwas evaporated
  5. additionThen, 6 N HCl was added
  6. extractionthe reaction mixture was extracted with EtOAc (3×10 mL)
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-6152c4e8b53f48b0be334f10cc6073f3
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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