Water → HCID 68186192, compound

HRID 537556Notes

Reaction equation

HRID 537556 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([CH3:41])[C:31]=1[N:32]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[N:33]1)[O:5][CH:6]([CH:23]1[CH2:26][C:25]([CH3:28])([CH3:27])[CH2:24]1)[C:7]1[CH:22]=[CH:21][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O:18]CC)=[O:17])=[O:12])=[CH:9][CH:8]=1.O.O1CCCC1.[OH-].[Na+]>C(Cl)Cl.C1(C)C=CC=CC=1.CO>[CH3:41][C:30]1[CH:29]=[C:4]([CH:3]=[C:2]([CH3:1])[C:31]=1[N:32]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[N:33]1)[O:5][CH:6]([CH:23]1[CH2:26][C:25]([CH3:28])([CH3:27])[CH2:24]1)[C:7]1[CH:8]=[CH:9][C:10]([C:11]([NH:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[O:12])=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 68157872HCID 68157872, compound

Product 1

HCID 68186192HCID 68186192, compoundYield 101.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a flask containing ethyl 3-(4-((3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)(3,3-dimethylcyclobutyl)methyl)benzamido)propanoate (100 mg, 0.180 mmol) was added water (0.437 mL), tetrahydrofuran (0.437 mL), and methanol (0.437 mL). Sodium hydroxide (36.1 mg, 0.880 mmol) was then added. The suspension was stirred at room temperature for 18 hours. The reaction was quenched with 1 N hydrochloric acid to pH 3 and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give 108 mg of crude material. The crude material was azeotrophed three times with toluene and three times with methylene chloride and then dried in vacuo for 18 h to provide (+/−)-3-(4-((3,5-dimethyl-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)(3,3-dimethylcyclobutyl)methyl)benzamido)propanoic acid (99.0 mg, 100%) as a solid. 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.71 (d, J=8.2 Hz, 2H), 7.65 (s, 1H), 7.36 (d, J=8.4 Hz, 2H), 6.76 (t, J=6.2 Hz, 1H), 6.56 (s, 2H), 5.01 (d, J=7.0 Hz, 1H), 3.72 (q, J=5.9 Hz, 2H), 2.74-2.59 (m, 3H), 1.88 (s, 6H), 1.87-1.68 (m, 3H), 1.68-1.58 (m, 1H), 1.13 (s, 3H), 1.10 (s, 3H). MS (M+1): 544.3.

Workup

  1. customThe reaction was quenched with 1 N hydrochloric acid to pH 3
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give 108 mg of crude material
  7. customdried in vacuo for 18 h

Sources & evidence

ORD record
ord-56befdf316714f4d993039c136883c1d
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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