Toluene → tert-Butyl 4-(5-(hydroxymethyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate

HRID 1045715Notes

Reaction equation

HRID 1045715 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]3[N:16]([CH:24]=[N:25][N:26]=3)[C:17]([C:20](OC)=[O:21])=[CH:18][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1>C(Cl)Cl>[OH:21][CH2:20][C:17]1[N:16]2[CH:24]=[N:25][N:26]=[C:15]2[C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)=[N:19][CH:18]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 21225700DiisobutylaluminumhydrideHCID 58447003Methyl 8-(4-(tert-butoxycarbonyl)piperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylate

Product 1

HCID 58447010tert-Butyl 4-(5-(hydroxymethyl)-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylateYield 50.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A 250 mL 3-necked round bottom flask was charged with methyl 8-(4-(tert-butoxycarbonyl)piperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylate (3.0 g, 8.3 mmol) and dry CH2Cl2 (30 mL). To the above was added dropwise a solution of 1.5 M diisobutylaluminum hydride in toluene (11 mL, 16.5 mmol) at −78° C. The resulting mixture was stirred at −78° C. for further 1 h then quenched by slow addition of methanol (10 mL). The mixture was poured into saturated aqueous NH4Cl (200 mL) and extracted with ethyl ether (100 mL×2). The combined organic layers were washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 3% MeOH in CH2Cl2, to afford 1.4 g (50%) of the product as a white solid. MS m/z: 335 (M+H+).

Workup

  1. customthen quenched by slow addition of methanol (10 mL)
  2. additionThe mixture was poured into saturated aqueous NH4Cl (200 mL)
  3. extractionextracted with ethyl ether (100 mL×2)
  4. washThe combined organic layers were washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was further purified by flash column chromatography on silica gel with 3% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-f7d1f37fa1aa454c81b29a4c403fca61
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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