Water → HCID 90405525, compound

HRID 924273Notes

Reaction equation

HRID 924273 reaction equation
[F:1][C:2]([F:27])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:16]=[C:17]([CH2:21][CH2:22][C:23](O)=[O:24])[CH:18]=[CH:19][CH:20]=3)=[N:11]2)=[CH:6][CH:5]=1.[H-].[Li+].[Al+3].[H-].[H-].[H-].O>O1CCCC1>[F:27][C:2]([F:1])([F:26])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:16]=[C:17]([CH2:21][CH2:22][CH2:23][OH:24])[CH:18]=[CH:19][CH:20]=3)=[N:11]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 21226445Aluminium lithium hydrideHCID 90404694HCID 90404694, compound

Product 1

HCID 90405525HCID 90405525, compoundYield 94.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 500 mL round bottomed flask 3-(3-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propanoic acid (CA13) (5.68 g, 15.1 mmol) was dissolved in tetrahydrofuran (151 mL). The reaction was cooled in an ice water bath and placed under inert atmosphere. Aluminum(III) lithium hydride (2.0 M in tetrahydrofuran, 15.8 mL, 31.6 mmol) was added dropwise. The reaction was allowed to gradually warm to room temperature and stir overnight. The reaction was cooled in an ice bath and water (1.2 mL) was added dropwise to quench excess aluminum(III) lithium hydride, the reaction mixture was allowed to stir for 1 hour. Then sodium hydroxide (15 wt %, 1.2 mL) was added dropwise. The reaction was allowed to stir for 1 hour. Then water (3.6 mL) was added. The resulting precipitate was removed via filtration. The filtrate was concentrated to give a yellow solid (5.20 g). The solid was purified by flash column chromatography using 0-60% ethyl acetate/hexanes as eluent providing the title compound as a white solid (4.01 g, 72%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.18-8.04 (m, 2H), 7.99-7.89 (m, 2H), 7.68-7.57 (m, 2H), 7.43 (t, J=7.6 Hz, 1H), 7.32 (dt, J=7.7, 1.5 Hz, 1H), 4.51 (t, J=5.2 Hz, 1H), 3.45 (td, J=6.4, 5.1 Hz, 2H), 2.71 (dd, J=8.8, 6.7 Hz, 2H), 1.87-1.70 (m, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.97; ESIMS m/z 364 ([M+H]+).

Workup

  1. temperatureThe reaction was cooled in an ice water bath
  2. temperatureThe reaction was cooled in an ice bath
  3. customto quench excess aluminum(III) lithium hydride
  4. stirringto stir for 1 hour
  5. additionThen sodium hydroxide (15 wt %, 1.2 mL) was added dropwise
  6. stirringto stir for 1 hour
  7. additionThen water (3.6 mL) was added
  8. customThe resulting precipitate was removed via filtration
  9. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-de4f0551a02346569e2ee50fb1d8571b
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Reaction notes

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