tert-Butyl 2-(methoxy(methyl)amino)-1-methyl-2-oxoethylcarbamate → HCID 11482058, compound

HRID 2054781Notes

Reaction equation

HRID 2054781 reaction equation
CON(C)[C:4]([CH:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH3:7])=[O:5].[C:17]1([Mg]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[O:5]=[C:4]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH3:7]

Participants

4

Reactant 2

HCID 375613tert-Butyl 2-(methoxy(methyl)amino)-1-methyl-2-oxoethylcarbamateHCID 178418255HCID 178418255, compound

Product 1

HCID 11482058HCID 11482058, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-butyl 1-(N-methoxy-N-methylcarbamoyl)ethylcarbamate (39) (2.3 g, 10.0 mmol, 1.0 equiv.) was added to a 250 mL RBF followed by THF (100 mL). The mixture was cooled to 0° C. via an ice bath and a 1.0 M solution of PhMgBr in THF (30.0 mL, 30.0 mmol, 3.0 equiv.) was added over 8 min. The reaction stirred for 1.0 h at 0° C. and the ice bath was removed. The reaction stirred for an additional 1.0 h at rt. and was again cooled to 0° C. via an ice bath. Next, the reaction was quenched by addition of 1.0 M HCl (60 mL). The solution was transferred to a separatory funnel with additional 1.0 M HCl (40 mL) and extracted with EtOAc (3×75 mL). The organic layers were combined, washed with sat. NaCl (1×50 mL), and dried over Na2SO4. The solution was then concentrated on a rotary evaporator and dried under vacuum to give 3.1 g of crude material. The residue was purified by flash column chromatography (15% EtOAc/Hexanes) to give 2.2 g (86%) of 40 as a colorless oil.10 Rf=0.25 (15% EtOAc/Hexanes); IR (film) 3356, 2977, 1680, 1164 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.96 (d, J=7.5 Hz, 2H, Ph-H), 7.59 (t, J=7.5 Hz, 1H, Ph-H), 7.48 (t, J=7.5 Hz, 2H, Ph-H), 5.62 (br d, J=6.5 Hz, 1H, carbamate-NH), 5.30 (t, 1H, Boc-NH—CH), 3.78 (s, 3H, N—OCH3), 3.19 (s, 3H, N—CH3), 1.46 (s, 9H, Boc-t-butyl-CH3, 1.40 (d, J=7.0 Hz, 3H, CH—CH3); 13C NMR (125 MHz, CDCl3) δ 199.6, 155.5, 134.3, 133.9, 129.0, 128.8, 80.0, 51.3, 28.6, 20.1; LRMS (ESI-MS m/z): Mass calcd for C14H19NO3 [2M]+, 498.62. Found 499. Spectroscopic data were consistent with the literature data for this compound.

Workup

  1. customthe ice bath was removed
  2. stirringThe reaction stirred for an additional 1.0 h at rt
  3. temperatureand was again cooled to 0° C. via an ice bath
  4. customNext, the reaction was quenched by addition of 1.0 M HCl (60 mL)
  5. customThe solution was transferred to a separatory funnel with additional 1.0 M HCl (40 mL)
  6. extractionextracted with EtOAc (3×75 mL)
  7. washwashed with sat. NaCl (1×50 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationThe solution was then concentrated on a rotary evaporator
  10. customdried under vacuum
  11. customto give 3.1 g of crude material
  12. customThe residue was purified by flash column chromatography (15% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-64f56610b658490d95887d83438846e7
Source dataset
uspto-grants-2008_02
Patent number
US07329775B2

Reaction notes

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