Diisopropylamine → HCID 178494652, compound

HRID 380397Notes

Reaction equation

HRID 380397 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[N:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1.[CH3:20][O:21][C:22]1[C:27]2[N:28]=[C:29]([CH2:31][O:32][CH3:33])[NH:30][C:26]=2[C:25]([C:34](OC)=[O:35])=[CH:24][CH:23]=1>O1CCCC1.CCCCCC>[CH3:20][O:21][C:22]1[C:27]2[N:28]=[C:29]([CH2:31][O:32][CH3:33])[NH:30][C:26]=2[C:25]([C:34](=[O:35])[CH2:19][C:16]2[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 79634-MethylpyridineHCID 178418339ButyllithiumHCID 178494654HCID 178494654, compound

Product 1

HCID 178494652HCID 178494652, compoundYield 25.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (1.51 g) in tetrahydrofuran (15 ml), under nitrogen, cooled to −10° C. was treated with butyl lithium in hexane (6 ml, 2.5M). The solution was cooled to −78° C. then treated dropwise with a solution of 4-picoline (1.40 g) in tetrahydrofuran (10 ml) followed by a solution of methyl 7-methoxy-2-methoxymethyl-3H-benzimidazole-4-carboxylate [1.25 g, Reference Example 3(a)] in tetrahydrofuran (15 ml). The brown solution was allowed to warm to room temperature and the resulting yellow suspension was filtered. The insoluble material was washed with a little tetrahydrofuran then air dried. The yellow solid (2.3 g) was dissolved in water (75 ml) and the solution extracted three times with dichloromethane (25 ml). The combined extracts were dried over magnesium sulphate and then evaporated. The resulting yellow solid (1.53 g) was subjected to flash chromatography on silica eluting initially with a mixture of methanol and dichloromethane (5:95, v/v) to give 1-(7-methoxy-2-methoxymethyl-3H-benzimidazol-4-yl)-2-(4-pyridyl)ethanone (0.39 g) recrystallised from toluene as a yellow solid, m.p. 218-220° C. with decomposition. [Elemental analysis:—C,66.58; H,5.53; N,13.76%. Calculated:—C,66.45; H,5.50; N,13.5%]; then eluting with a mixture of methanol and dichloromethane (1:9, v/v) to give 1,3-bis-(4-pyridyl)-2-(7-methoxy-2-methoxymethyl-3H-benzimidazol-4-yl)-propan-2-ol (0.4 g) recrystallised from methanol as a white solid, m.p. 210° C. with decomposition. [Elemental analysis:—C,68.40; H,5.94; N,13.85%. Calculated:—C,68.30; H,5.98; N,14.00%].

Workup

  1. temperatureto warm to room temperature
  2. filtrationthe resulting yellow suspension was filtered
  3. washThe insoluble material was washed with a little tetrahydrofuran
  4. customair dried
  5. dissolutionThe yellow solid (2.3 g) was dissolved in water (75 ml)
  6. extractionthe solution extracted three times with dichloromethane (25 ml)
  7. dry with materialThe combined extracts were dried over magnesium sulphate
  8. customevaporated
  9. additionThe resulting yellow solid (1.53 g) was subjected to flash chromatography on silica eluting initially with a mixture of methanol and dichloromethane (5:95

Sources & evidence

ORD record
ord-c67b5df3e2cd4c09ac9ef6e67740e31b
Source dataset
uspto-grants-2001_10
Patent number
US06303600B1

Reaction notes

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