Ammonium Chloride → benzyl [(1S)-1-methyl-2-(1-methyl-1H-imidazol-4-yl)-2-oxoethyl]carbamate

HRID 1994576Notes

Reaction equation

HRID 1994576 reaction equation
CON(C)[C:4](=[O:18])[C@@H:5]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:6].C([Mg]Cl)(C)C.C([Mg]Br)C.I[C:30]1[N:31]=[CH:32][N:33]([CH3:35])[CH:34]=1.[NH4+].[Cl-]>C(Cl)Cl.C1COCC1.CCOCC.O>[CH3:6][C@H:5]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:4]([C:30]1[N:31]=[CH:32][N:33]([CH3:35])[CH:34]=1)=[O:18]

Participants

10

Reactant 5

HCID 25517Ammonium ChlorideHCID 27734634-Iodo-1-methyl-1H-imidazoleHCID 10515879(S)-Benzyl 1-(methoxy(methyl)amino)-1-oxopropan-2-ylcarbamateHCID 178418443HCID 178418443, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 59135236benzyl [(1S)-1-methyl-2-(1-methyl-1H-imidazol-4-yl)-2-oxoethyl]carbamate

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of benzyl {(1S)-2-[methoxy(methyl)amino]-1-methyl-2-oxoethyl}carbamate (64 mg, 0.24 mmol) in CH2Cl2 (1 mL) was cooled to −20° C. under N2, and isopropylmagnesium chloride (120 μL of a 2.0 M solution in THF) was added dropwise. The mixture was stirred at −20° C. for 20 min. In a separate flask ethylmagnesium bromide (480 μL of a 2.0 M solution in Et2O) was added to a solution of 4-iodo-1-methyl-1-H-imidazole (109 mg, 0.48 mmol) in dry CH2Cl2 (1.5 mL) at room temperature. The resulting mixture was stirred for 20 min and then added by cannula to the solution above slowly. The resulting solution was left to stir overnight. Saturated NH4Cl was added to the reaction solution. The mixture was diluted with water and the aqueous phase was extracted with CH2Cl2 (2×25 mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Flash chromatography of the residue yielded benzyl [(1S)-1-methyl-2-(1-methyl-1H-imidazol-4-yl)-2-oxoethyl]carbamate. LCMS calc.=288.14; found=288.3 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.65 (s, 1H); 7.47 (s, 1H); 7.35-7.28 (m, 5H); 5.93 (d, J=6.9 Hz, 1H); 5.29-5.25 (m, 1H); 5.13 (s, 2H); 3.73 (s, 3H); 1.26 (d, J=7.1 Hz, 3H).

Workup

  1. stirringThe resulting mixture was stirred for 20 min
  2. additionadded by cannula to the solution above slowly
  3. waitThe resulting solution was left
  4. stirringto stir overnight
  5. extractionthe aqueous phase was extracted with CH2Cl2 (2×25 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cbd5e6e25ba5479e877189dba05becf9
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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