Sodium hydride → HCID 22676828, compound

HRID 1006248Notes

Reaction equation

HRID 1006248 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:12]2[Br:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[F:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:31][C:30]1[CH:33]=[CH:34][C:27]([F:26])=[CH:28][CH:29]=1)[C:13]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:12]2[Br:23])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 22676785HCID 22676785, compound

Product 1

HCID 22676828HCID 22676828, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 5-(benzyloxy)-3-bromo-1H-indole-2-carboxylate, Ref. WO96/18393 (6.77 g, 20.3 mmol, Ref. 96/18393) in N,N-dimethylformamide (10+5 mL rinse) was added slowly (10 min) to a cooled (0° C.) and stirred suspension of sodium hydride (0.72 g, 30 mmol) in N,N-dimethylformamide (30 mL). The reaction was stirred for 1 h and then 4-fluorobenzylbromide (3.7 mL, 5.7 g, 30 mmol) was added. The cold bath was removed and the mixture was stirred for 18 h. The reaction was quenched by pouring over ice water (400 mL) and then the product was extracted with ethyl acetate (3×100 mL). 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 50% dichloromethane/hexane gave 6.80 g (75%) of the desired product containing trace impurities. The product had: 1H NMR (300 MHz, CDCl3) δ 6.84-7.53 (m, 12 H), 5.72 (s, 2 H), 5.13 (s, 2 H), 4.38 (q, 2 H), 1.40 (t, 3 H).

Workup

  1. stirringThe reaction was stirred for 1 h
  2. customThe cold bath was removed
  3. stirringthe mixture was stirred for 18 h
  4. customThe reaction was quenched
  5. additionby pouring over ice water (400 mL)
  6. extractionthe product was extracted with ethyl acetate (3×100 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-e6a58a3787b646e091732507c23a8547
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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