Ethyl Acetate → (R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1482981Notes

Reaction equation

HRID 1482981 reaction equation
[CH:1]([C@H:4]1[N:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:7][N:6]2[C:17]3[CH:23]=[C:22]([S:24]([CH3:27])(=[O:26])=[O:25])[C:21]([C:28](OC)=[O:29])=[CH:20][C:18]=3[N:19]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.CCOC(C)=O>C(Cl)Cl>[OH:29][CH2:28][C:21]1[C:22]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:23][C:17]2[N:6]3[CH2:7][CH2:8][N:9]([C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[C@H:4]([CH:1]([CH3:2])[CH3:3])[C:5]3=[N:19][C:18]=2[CH:20]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydrideHCID 89815749(R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8 (1H)-dicarboxylate

Product 1

HCID 89815566(R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylateYield 74.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a 50 mL three-necked flask containing (R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8(1H)-dicarboxylate (250 mg, 0.554 mmol, from preparation 2) in DCM (5 mL) was added DIBAL-H (1.70 mL, 1.67 mmol, 1.0 M in toluene) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 3 h. The reaction was quenched with sat. aq. ammonium chloride (10 mL) at −78° C. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (15 mL) and brine, and then dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with PE:EtOAc 8:1˜2:1 to give (R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate (175 mg, 74.1% yield) as a white solid.

Workup

  1. customThe reaction was quenched with sat. aq. ammonium chloride (10 mL) at −78° C
  2. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with water (15 mL) and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with PE

Sources & evidence

ORD record
ord-a21f20b86625463e8f0e0034f5b231ae
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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