Water → HCID 86686447, compound

HRID 2176815Notes

Reaction equation

HRID 2176815 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:20]([C:25]1C=C(C)C=C[C:26]=1S([O-])(=O)=O)[CH2:21][CH2:22]CC.O>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]([CH:21]([CH2:20][CH2:25][CH3:26])[CH3:22])[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 146245-BenzyloxyindoleHCID 24758Sodium hydrideHCID 20192300HCID 20192300, compound

Product 1

HCID 86686447HCID 86686447, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Benzyloxyindole (7) (8.81 g, 39.5 mmol, 1.0 equiv., supplied by Combi-Blocks) was dissolved in anhydrous DMF (100 mL) and the solution was cooled to 0° C. Dry sodium hydride (1.89 g, 78.9 mmol, 2.0 equiv.) was added slowly. The mixture was warmed to room temperature over 30 minutes. 2-Pentyl-tosylate was added dropwise. The mixture was stirred for 18 h. Water was added slowly (dropwise at first) to quench excess NaH. The resulting mixture was extracted once with ether, and then washed with water and brine, respectively. The organic phase was dried with MgSO4, and concentrated on a rotary evaporator to yield a crude oil. The crude product was purified by flash column chromatography (3:1 hexanes/ethyl acetate) to yield 5-(benzyloxy)-1-(pentan-2-yl)-1H-indole (8) as an amber oil (10.67 g) of approximately 90% purity, which was used in the next step without any further purification. 1H NMR (500 MHz, CDCl3) δ7.50 (d, J=7.3 Hz, 2H), 7.40 (t, J=7.3 Hz, 2H), 7.34 (d, J=7.3 Hz, 1H), 7.29 (d, J=9.0 Hz, 1H), 7.17 (dd, J=8.9, 2.4 Hz, 1H), 6.96 (dd, J=8.9, 2.4 Hz, 1H), 6.44 (d, J=3.1 Hz, 1H), 5.12 (s, 2H), 4.44 (m, 1H), 1.88 (m, 1H), 1.77 (m, 1H), 1.50 (d, J=6.8 Hz, 3H), 1.23 (m, 2H), 0.89 (t, J=7.4 Hz, 3H).

Workup

  1. temperatureThe mixture was warmed to room temperature over 30 minutes
  2. customto quench excess NaH
  3. extractionThe resulting mixture was extracted once with ether
  4. washwashed with water and brine
  5. dry with materialThe organic phase was dried with MgSO4
  6. concentrationconcentrated on a rotary evaporator
  7. customto yield a crude oil
  8. customThe crude product was purified by flash column chromatography (3:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-ccb917c8b06b4d36b5d9db6f2c1d7f72
Source dataset
uspto-grants-2015_06
Patent number
US09067886B2

Reaction notes

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