Acetic Anhydride → {[6-(1-Acetyl-3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetonitrile

HRID 495503

Reaction equation

HRID 495503 reaction equation
[CH2:1]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]=1[C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[CH:21]=[C:20]([O:25][CH2:26][C:27]#[N:28])[CH:19]=[CH:18]2)[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:29][C:30](OC(C)=O)=[O:31].CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O>>[C:30]([N:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])=[C:7]1[C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[CH:21]=[C:20]([O:25][CH2:26][C:27]#[N:28])[CH:19]=[CH:18]2)(=[O:31])[CH3:29]

Participants

4

Reactant 3

HCID 7918Acetic AnhydrideHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-2×HCID 11337627{[6-(3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetonitrile

Product 1

HCID 22327348{[6-(1-Acetyl-3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetonitrileYield 49.1%

Conditions

Temperature
70 °C

Procedure

To a stirred solution of {[6-(3-pentyl-1H-indol-2-yl)-2-naphthyl]oxy}acetonitrile (0.300 g, 0.814 mmol) in Ac2O (3 mL, 3.18 mmol) at rt was added a catalytic amount of CSA (0.019 g, 0.0814 mmol). The reaction was heated to 70° C. for 18 h, and by TLC the reaction was about one half complete. Another 19 mg of CSA added and kept at 70° C. for an additional 24 h. After this time, the reaction mixture was quenched with 1 N HCl (˜2 mL). The resulting solution was extracted with EtOAc (100 mL). The organic layer was washed with 1 N HCl (10 mL), sat. aq. NaHCO3 (10 mL), and brine (10 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc:petroleum ether gradient) to afford the product (0.164 g, 49%) as a solid; 1H NMR (DMSO-d6) δ 0.73 (t, J=7.2 Hz, 3H), 1.03-1.23 (m, 4H), 1.47-1.61 (m, 2H), 1.92 (s, 3H), 3.24-3.42 (m, 2H), 5.34 (s, 2H), 7.27-7.43 (m, 3H), 7.52-7.70 (m, 3H), 7.94-8.08 (m, 3H), 8.33 (d, J=8.8 Hz, 1H); mass spectrum [(+) ESI], m/z 411 (M+H)+, 433 (M+Na)+.

Workup

  1. customAfter this time, the reaction mixture was quenched with 1 N HCl (˜2 mL)
  2. extractionThe resulting solution was extracted with EtOAc (100 mL)
  3. washThe organic layer was washed with 1 N HCl (10 mL), sat. aq. NaHCO3 (10 mL), and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationAfter concentration
  6. customthe residue was purified by the Biotage Flash 40 apparatus (10 to 20% EtOAc:petroleum ether gradient)

Sources & evidence

ORD record
ord-f0615098cbce4c64813d8790d9f69d6b
Source dataset
uspto-grants-2005_09
Patent number
US06939886B2

Linked notes

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