Sodium hydride → 5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indole

HRID 717515Notes

Reaction equation

HRID 717515 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]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[C:12]2[CH3:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[I:35][C:36]1[CH:43]=[CH:42][C:39]([CH2:40]Br)=[CH:38][CH:37]=1>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:40][C:39]1[CH:42]=[CH:43][C:36]([I:35])=[CH:37][CH:38]=1)[C:13]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:20][CH:19]=1)=[C:12]2[CH3:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 9542584-Iodobenzyl bromideHCID 38247451H-Indole, 3-methyl-5-(phenylmethoxy)-2-[4-(phenylmethoxy)phenyl]-

Product 1

HCID 120740765-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indoleYield 31.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole (4.2 g, 10 mmol; see PCT/US98/21609 for synthesis) in DMF (40 mL) was cooled to 0° C. under nitrogen atmosphere. Sodium hydride (60% dispersion in mineral oil; 420 mg, 10.5 mmol) was added in one portion. The reaction mixture was stirred at 0° C. for 5 min, and then ice bath was removed and allowed to warm to room temperature. After 1 h, the reaction was cooled back to 0° C. and 4-iodobenzyl bromide (3.7 g, 12.5 mmol) was added slowly. After 5 minutes, the ice bath was removed and the reaction mixture was stirred at room temperature for 6 h. The reaction was diluted with water (200 mL), and ethyl acetate. The precipitate was sonicated, filtered off and dried to give 1.99 g of the desired product. The filtrate was extracted with ethyl acetate (50 mL), the organic layer was washed with water, washed with brine and dried (MgSO4), filtered, concentrated and purified by silica gel chromatography (20%-70% DCM in hexanes) to afford 2.62 g. The reaction resulted in total 4.6 g of 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-iodobenzyl)-3-methyl-1H-indole as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.56 (d, 2H), 7.51-7.46 (m, 4H), 7.44-7.38 (m, 4H), 7.38-7.32 (m, 2H), 7.29 (d, 2H), 7.16 (d, 1H), 7.16-7.10 (m, 3H), 6.82 (dd, 1H), 6.62 (d, 2H), 5.20 (s, 2H), 5.14 (d, 4H), 2.17 (s, 3H).

Workup

  1. customice bath was removed
  2. temperatureto warm to room temperature
  3. waitAfter 1 h
  4. temperaturethe reaction was cooled back to 0° C.
  5. waitAfter 5 minutes
  6. customthe ice bath was removed
  7. stirringthe reaction mixture was stirred at room temperature for 6 h
  8. additionThe reaction was diluted with water (200 mL), and ethyl acetate
  9. customThe precipitate was sonicated
  10. filtrationfiltered off
  11. customdried

Sources & evidence

ORD record
ord-a57ef076e8ea410e87f35055205a9690
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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