Iodoethane → HCID 22676740, compound

HRID 1006264Notes

Reaction equation

HRID 1006264 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH2:22][CH2:23][OH:24])[CH:19]=4)[N:14]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=4)[C:13]=3[C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:9]=[CH:10][CH:11]=2)[CH2:3][CH2:2]1.[H-].[Na+].[CH2:41](I)[CH3:42]>CN(C)C=O>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH2:22][CH2:23][O:24][CH2:41][CH3:42])[CH:19]=4)[N:14]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=4)[C:13]=3[C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:9]=[CH:10][CH:11]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 22676727HCID 22676727, compound

Product 1

HCID 22676740HCID 22676740, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 3-[3-(cyclopropylmethoxy)phenyl]-5-(2-hydroxyethoxy)-1-(3-methoxybenzyl)-1-H-indole-2-carboxylate (Example 223, 110 mg, 0.23 mmol) was added to a cooled (0° C.) and stirred suspension of sodium hydride (12 mg, 0.50 mmol) in N,N-dimethylformamide (5 mL). The cold bath was removed and the reaction was stirred for 1 h. Ethyl iodide (80 μL, 156 mg, 1.0 mmol) was added and the reaction was stirred for an additional hour. The reaction was quenched with methanol (1 mL) and then diluted with water (50 mL). The product was extracted with ethyl acetate (3×30 mL) and then the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 4:1 hexane/ethyl acetate gave 62 mg (50%) of product. The product had: 1H NMR (300 MHz, acetone-D6) δ 7.42 (d, 1 H), 7.29-7.36 (m, 2 H), 7.14 (dd, 1 H), 6.94-7.02 (m, 4 H), 6.63-6.79 (m, 3 H), 5.78 (s, 2 H), 3.99-4.12 (m, 4 H), 3.86 (d, 2 H), 3.64-3.71 (m, 5 H), 3.48 (q, 2 H), 1.24-1.34 (m, 1 H), 1.11 (t, 3 H), 0.98 (t, 3 H), 0.54-0.64 (m, 2 H), 0.32-0.42 (m, 2 H).

Workup

  1. customThe cold bath was removed
  2. stirringthe reaction was stirred for 1 h
  3. stirringthe reaction was stirred for an additional hour
  4. customThe reaction was quenched with methanol (1 mL)
  5. additiondiluted with water (50 mL)
  6. extractionThe product was extracted with ethyl acetate (3×30 mL)
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea835b547a504dd980fa7560a6a01e0d
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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