Diisobutylaluminumhydride → (1-(2-chloro-5-fluoropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanol

HRID 469173Notes

Reaction equation

HRID 469173 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([C:13](OCC)=[O:14])[C:10]([CH3:18])=[N:9]2)[C:5]([F:19])=[CH:4][N:3]=1.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH2:13][OH:14])[C:10]([CH3:18])=[N:9]2)[C:5]([F:19])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 86659253ethyl 1-(2-chloro-5-fluoropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate

Product 1

HCID 58513701(1-(2-chloro-5-fluoropyrimidin-4-yl)-3-methyl-1H-pyrazol-4-yl)methanolYield 90%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 1-(2-chloro-5-fluoropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate 1 (4.9 g, 17.2 mmol) in 60 mL of anhydrous tetrahydrofuran (THF), was slowly added 38 mL (38 mmol) of 1M solution of di-isobutylaluminum hydride (DIBAL) in toluene with ice bath cooling. After being stirred for 2 hours at the same temperature, the reaction was quenched by slow addition of 1N-NaOH solution. It was diluted with ethyl acetate and washed with brine. The collected organic layer was dried over anhydrous sodium sulfate and then partially concentrated in vacou. To this, n-hexanes were added to form pale yellow precipitates. The resulting solids were collected by filtration and rinsed with n-hexanes and then dried with high vacuum to give 3.7 g (90%) of Intermediate No. 2; 1H NMR (300 MHz, CDCl3) δ 8.57 (1H, d, J=3.3 Hz), 8.52 (1H, s), 7.94 (1H, s), 4.72 (2H, s); MS (ESI) m/z 243 [M+H]+.

Workup

  1. temperaturecooling
  2. customthe reaction was quenched by slow addition of 1N-NaOH solution
  3. additionIt was diluted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe collected organic layer was dried over anhydrous sodium sulfate
  6. concentrationpartially concentrated in vacou
  7. additionTo this, n-hexanes were added
  8. customto form pale yellow precipitates
  9. filtrationThe resulting solids were collected by filtration
  10. washrinsed with n-hexanes
  11. customdried with high vacuum

Sources & evidence

ORD record
ord-8a608183a9304bb998814a65e9bddd04
Source dataset
uspto-grants-2014_01
Patent number
US08629132B2

Reaction notes

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