4-Fluorobenzoyl chloride → 5-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazine

HRID 1773788Notes

Reaction equation

HRID 1773788 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[O:15]([CH2:22][C:23]1[CH:31]=[C:26]2[CH:27]=[N:28][CH2:29][CH2:30][N:25]2[N:24]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[F:32][C:33]1[CH:41]=[CH:40][C:36]([C:37]([N:28]2[CH2:29][CH2:30][N:25]3[N:24]=[C:23]([CH2:22][O:15][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:31]=[C:26]3[CH2:27]2)=[O:38])=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 678794-Fluorobenzoyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 679583882-Phenoxymethyl-6,7-dihydro-pyrazolo[1,5-a]pyrazine

Product 1

HCID 679583635-(4-Fluorobenzoyl)-4,5,6,7-tetrahydro-2-(phenoxymethyl)-pyrazolo[1,5-a]pyrazineYield 87.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

Sodium triacetoxyborohydride (20.8 mg, 0.093 mmol) was added to a stirred solution of 2-phenoxymethyl-6,7-dihydro-pyrazolo[1,5-a]pyrazine (15 mg, 0.062 mmol) in DCM (0.5 mL). The mixture was stirred at room temperature for 16 hours and then, 4-fluorobenzoyl chloride (0.011 mL, 0.093 mmol) was added and the mixture stirred at room temperature for 1 hour. The mixture was diluted with a saturated solution of Na2CO3 and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50). The desired fractions were collected and the solvents evaporated in vacuo to yield rac-(4-fluoro-phenyl)-(2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanone (19 mg, 84% yield) as a colourless oil that precipitated upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 1.56 (d, J=6.9 Hz, 3H), 3.59 (br. s., 1H), 4.34 (br. s., 1H), 4.05-4.22 (m, 1H), 4.22-4.32 (m, 1H), 5.04 (s, 2H), 5.58 (br. s., 1H), 6.15 (br. s., 1H), 6.96 (t, J=7.4 Hz, 1H), 7.00 (d, J=7.8 Hz, 2H), 7.10-7.20 (m, 2H), 7.27-7.34 (m, 2H), 7.40-7.49 (m, 2H).

Workup

  1. stirringthe mixture stirred at room temperature for 1 hour
  2. extractionextracted with DCM
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 50/50)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-c2a18ecf27f94b028b4c6f3bdf31e37b
Source dataset
uspto-grants-2016_02
Patent number
US09255103B2

Reaction notes

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