(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamate → HCID 59135130, compound

HRID 1994577Notes

Reaction equation

HRID 1994577 reaction equation
[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CON(C)[C:23](=[O:37])[C@@H:24]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:25].C([Mg]Cl)(C)C>C1COCC1>[CH2:1]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][N:12]=[C:11]1[C:23](=[O:37])[C@@H:24]([NH:26][C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 10515879(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 147959081-BenzyloxymethylimidazoleHCID 178418339ButyllithiumHCID 178418918HCID 178418918, compound

Product 1

HCID 59135130HCID 59135130, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-[(benzyloxy)methyl]-1H-imidazole (706 mg, 3.75 mmol) in THF (4 mL) at −78° C. under N2, was added n-Butyllithium (2.3 mL of a 1.6 M solution in hexanes). The mixture was stirred at −78° C. for 30 min. To a solution of benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate (200 mg, 0.75 mmol) in THF (2 mL) under N2 at −15° C., was added isopropylmagnesium chloride (375 μL of a 2.0 M solution in THF). The resulting mixture was stirred at −15° C. for 15 min. This mixture was then added, by cannula to the solution above at −78° C. The mixture stirred at −78° C. for about 3 h, then warmed up gradually to room temperature and stirred overnight. The mixture was quenched with saturated NH4Cl. The aqueous layer was extracted with CH2Cl2 (3×25 mL). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography to afford benzyl ((1S)-2-{1-[(benzyloxy)methyl]-1H-imidazol-2-yl}-1-methyl-2-oxoethyl)carbamate contaminated with about 30% of the unreacted starting material benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate. The mixture was carried forward to the next step without further purification. LCMS calc.=394.18; found=394.2 (M+1)+.

Workup

  1. stirringThe resulting mixture was stirred at −15° C. for 15 min
  2. additionThis mixture was then added, by cannula to the solution above at −78° C
  3. stirringThe mixture stirred at −78° C. for about 3 h
  4. temperaturewarmed up gradually to room temperature
  5. stirringstirred overnight
  6. customThe mixture was quenched with saturated NH4Cl
  7. extractionThe aqueous layer was extracted with CH2Cl2 (3×25 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a583e8c3f92347df933c211a502704e5
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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