Sodium hydride → (Z)-4-(2-(naphthalen-1-yl)vinyl)-1-(pentan-2-yl)-1H-indole

HRID 2176809Notes

Reaction equation

HRID 2176809 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1)(=O)OCC)C.[CH3:22][CH:23]([N:27]1[C:35]2[CH:34]=[CH:33][CH:32]=[C:31]([CH:36]=O)[C:30]=2[CH:29]=[CH:28]1)[CH2:24][CH2:25][CH3:26]>COC>[C:12]1(/[CH:11]=[CH:36]\[C:31]2[CH:32]=[CH:33][CH:34]=[C:35]3[C:30]=2[CH:29]=[CH:28][N:27]3[CH:23]([CH2:24][CH2:25][CH3:26])[CH3:22])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 101271Diethyl P-(1-naphthalenylmethyl)phosphonateHCID 866864451-(pentan-2-yl)-1H-indole-4-carbaldehyde

Product 1

HCID 86686446(Z)-4-(2-(naphthalen-1-yl)vinyl)-1-(pentan-2-yl)-1H-indoleYield 50%

Reagents, catalysts & solvents 1

HCID 8254Dimethyl EtherSolvent2×

Procedure

To a suspension of 95% sodium hydride (NaH, 347 mg, 13.76 mmol) in dimethyl ether (DME, 17 mL) was added diethyl(naphthalen-1-ylmethyl)phosphonate (4) (960 mg, 3.44 mmol) dropwise at 0° C. The resulting solution was stirred at room temperature for 1 h, then semi-pure 1-(pentan-2-yl)-1H-indole-4-carbaldehyde (3) (˜3.44 mmol) in DME (2 mL) was added dropwise and the reaction mixture was stirred for 8 h at room temperature. After the reaction completed as indicated by thin layer chromatography, the reaction mixture was poured into ice-cold water (30 mL), extracted with ethyl acetate (3×30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography (6:1 hexane/ethyl acetate) gave (Z)-4-(2-(naphthalen-1-yl)vinyl)-1-(pentan-2-yl)-1H-indole (5) (580 mg, 1.70 mmol) in 50% yield. 1H NMR (CDCl3): 8.30 (d, 1H, J=8.0 Hz), 8.09 (d, 1H, J=16.0 Hz), 7.91 (dd, 1H, J=7.5, 1.5 Hz), 7.86 (d, 1H, J=7.0 Hz), 7.84 (d, 1H, J=8.0 Hz), 7.59 (d, 1H, J=16.0 Hz), 7.58-7.52 (m, 3H), 7.48 (d, 1H, J=7.0 Hz), 7.39 (d, 1H, J=8.0 Hz), 7.32 (d, 1H, J=3.5 Hz), 7.29 (d, 1H, J=7.5 Hz), 6.91 (d, 1H, J=3.0 Hz), 4.61-4.53 (m, 1H), 2.00-1.92 (m, 1H), 1.88-1.80 (m, 1H), 1.56 (d, 3H, J=7.0 Hz), 1.36-1.20 (m, 4H), 0.93 (t, 3H, J=7.5 Hz).

Workup

  1. stirringthe reaction mixture was stirred for 8 h at room temperature
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (6:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-a15e52cc7e024e3e91404af856d23fe5
Source dataset
uspto-grants-2015_06
Patent number
US09067886B2

Reaction notes

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