1-(diethoxymethyl)-1H-imidazole → HCID 14978579, compound

HRID 2256014Notes

Reaction equation

HRID 2256014 reaction equation
C(OC(OCC)[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)C.[C:13]([NH:16][CH:17](Br)[C:18]([NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])(=[O:15])[CH3:14]>C1COCC1>[C:13]([NH:16][CH:17]([C:6]1[NH:5][CH:9]=[CH:8][N:7]=1)[C:18]([NH:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])(=[O:15])[CH3:14]

Participants

4

Reactant 2

HCID 38495351-(diethoxymethyl)-1H-imidazoleHCID 14860701HCID 14860701, compound

Product 1

HCID 14978579HCID 14978579, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The 2-lithio salt solution of 1-diethoxymethylimidazole was added dropwise (15 min) into a cooled (-78° C.) THF solution (130 mL) of 2-acetamido-N-benzyl-2-bromoacetamide (prepared from 2-acetamido-N-benzyl-2-ethoxyacetamide (2.00 g, 8.0 mmol) and BBr3 (1M in CH2Cl2, 10 mL, 10.0 mmol)). The reaction was stirred at -78° C. (1 h) and then quenched with a saturated aqueous NH4Cl (50 mL) solution. The mixture was stirred at room temperature (30 min), and made basic ("pH" 9.2)by adding aqueous K2CO3. The aqueous mixture was extracted with EtOAc (3×100 mL), and the combined extracts were dried (Na2SO4). The solvents were removed in vacuo and the residue was purified by flash column chromatography on SiO2 gel (2.5% MeOH/CHCl3) to give 0.14 g (7%) of the desired product: mp 228°-230° C. (recrystallized from EtOH); Rf 0.46 (10% MeOH/CHCl3); IR (KBr) 3200 (br), 1610, 1500 (br), 1430, 1350, 740, 680 cm-1 ; 1H NMR (DMSO-d6) δ 1.91 (s, C(O)CH3), 4.29 (d, J=5.6 Hz, CH2), 5.51 (d, J=7.7 Hz, CH), 6.85 (br s, C4H), 7.05 (br s, C5H), 7.18-7.30 (m, 5 PhH), 8.42 (d, J=7.7 Hz, NH), 8.65 (t, J=5.6 Hz, NH), 11.91 (br s, NH); 13C NMR (DMSO-d6) 22.49 (C(O)CH3), 42.21 (CH2), 51.62 (CH), 126.60 (C4'), 126.98 (2C2' or 2C3'), 127.21 (C4), 128.09 (2C2' or 2C3'), 128.32 (C5), 139.05 (C1'), 143.74 (C2), 168.12 (C(O)NH), 169.30 (C(O)CH3) ppm; mass spectrum (FD) 273 (M+ +1, 65), 272 (M+, 100).

Workup

  1. customquenched with a saturated aqueous NH4Cl (50 mL) solution
  2. stirringThe mixture was stirred at room temperature (30 min)
  3. addition9.2)by adding aqueous K2CO3
  4. extractionThe aqueous mixture was extracted with EtOAc (3×100 mL)
  5. dry with materialthe combined extracts were dried (Na2SO4)
  6. customThe solvents were removed in vacuo
  7. customthe residue was purified by flash column chromatography on SiO2 gel (2.5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-af6069da2cc0499aac29cabe3d6c067f
Source dataset
uspto-grants-1997_08
Patent number
US05654301

Reaction notes

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