Water → 7-(2-Methyl-1,3-dioxolan-2-yl)-1-(4-(2-naphthyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)heptan-1-one

HRID 913056Notes

Reaction equation

HRID 913056 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[N:12]=[CH:13][N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=1.[Li]CCCC.CON(C)[C:32](=[O:45])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][C:39]1([CH3:44])[O:43][CH2:42][CH2:41][O:40]1.O>C1COCC1.CCCCCC>[CH3:44][C:39]1([CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][C:32]([C:13]2[N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:15]=[C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)[N:12]=2)=[O:45])[O:40][CH2:41][CH2:42][O:43]1

Participants

7

Reactant 4

HCID 962WaterHCID 673822734-(2-Naphthyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazoleHCID 86645337N-methoxy-N-methyl-7-(2-methyl-1,3-dioxolan-2-yl)heptanamideHCID 178418339Butyllithium

Product 1

HCID 673819037-(2-Methyl-1,3-dioxolan-2-yl)-1-(4-(2-naphthyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)heptan-1-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of E2 (1.0 eq.) in THF (0.1 M solution) at −78° C. was added a solution of n-BuLi (1.3 eq.) in hexane. The solution was stirred for 30 min and then a solution of N-methoxy-N-methyl-7-(2-methyl-1,3-dioxolan-2-yl)heptanamide (1.5 eq.) in THF was slowly added. The reaction mixture was stirred for 1 hr at −78° C. and then 1 hr at RT. Then water was added and the aqueous phase was extracted with EtOAc. The combined organic extracts were dried (MgSO4) and the solvent was removed under reduced pressure. The crude was purified by column chromatography on silica gel eluting with 20-50% EtOAc/petroleum ether to obtain E3 as yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.32 (1H, s), 7.96-7.81 (4H, m), 7.68 (1H, s) 7.53-7.42 (2H, m), 5.85 (2H, s), 3.92 (4H, s), 3.64 (2H, t, J=8.2 Hz), 3.26 (2H, t, J=8.2 Hz), 1.77 (2H, m), 1.69-1.36 (8H, m), 1.31 (3H, s), 0.97 (2H, t, J=8.2 Hz), 0.19 (9H, s). MS (ES) C30H42N2O4Si requires: 522, found: 523 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for 1 hr at −78° C.
  2. custom1 hr
  3. customat RT
  4. extractionthe aqueous phase was extracted with EtOAc
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customthe solvent was removed under reduced pressure
  7. customThe crude was purified by column chromatography on silica gel eluting with 20-50% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-57181833e29c4f529f880cba0a321863
Source dataset
uspto-grants-2011_09
Patent number
US08026265B2

Reaction notes

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