Sodium Carbonate → (R)-benzyl 2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-carboxylate

HRID 1482949Notes

Reaction equation

HRID 1482949 reaction equation
[CH2:1]([O:8][C:9](=[O:24])[NH:10][C@H:11]([CH:21]([CH3:23])[CH3:22])[C:12]([NH:14][CH2:15][CH:16](OC)OC)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.O.C([O-])([O-])=O.[Na+].[Na+]>>[CH:21]([C@@H:11]1[C:12](=[O:13])[NH:14][CH:15]=[CH:16][N:10]1[C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:24])([CH3:22])[CH3:23]

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 22392675Trifluoroacetic acid waterHCID 89827923(R)-benzyl (1-((2,2-dimethoxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate

Product 1

HCID 89827917(R)-benzyl 2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-carboxylateYield 95.4%

Procedure

(R)-benzyl(1-((2,2-dimethoxyethyl)amino)-3-methyl-1-oxobutan-2-yl)carbamate (335 g, 0.99 mol) was added in portions to a cooled TFA-H2O (temperature <5° C., VTFA VH2O=7/3, 2 L), and the solution was stirred at rt for 12 h. The solution was added slowly into a stirring cooled sat. aq. Na2CO3 (2.5 L) to keep the pH>8. Then the mixture was extracted with EtOAc (5×2 L). The combined organic layers were washed with brine (2 L), dried over anhydrous Na2SO4, filtered and evaporated in vacuo to give (R)-benzyl 2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-carboxylate as a white solid (259 g, 95.4%), which was used for next step without further purification. LC-MS m/z 274.9 [M+H]+. 1H NMR (CD3OD 300 MHz): δ7.36-7.34 (m, 5H), 6.33-6.30 (m, 1H), 5.79-5.68 (m, 1H), 5.26-5.13 (m, 2H), 4.38-4.29 (m, 1H), 2.01-1.96 (m, 1H), 1.00-0.84 (m, 6H).

Workup

  1. additionThe solution was added slowly into a stirring
  2. extractionThen the mixture was extracted with EtOAc (5×2 L)
  3. washThe combined organic layers were washed with brine (2 L)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-4a63fe516b564bf0a8e2905cf92f33f1
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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