Diethyl Ether → HCID 67515899, compound

HRID 1503140Notes

Reaction equation

HRID 1503140 reaction equation
[Li]C.C(OCC)C.OS([O-])(=O)=O.[K+].[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2/[C:25](/[C:33]#C)=[CH:26]/[C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1>CS(C)=O.C(Cl)Cl.CCO.C1COCC1>[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][CH:20]=[C:19]2[C:25]([CH3:33])=[CH:26][C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 516920Potassium bisulfateHCID 49853707HCID 49853707, compoundHCID 178418348HCID 178418348, compound

Product 1

HCID 67515899HCID 67515899, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 21584144Dichloromethane ethanolSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of MeLi in diethyl ether (5.1 mL, 1.6 M, 8.2 mmol, 6.0 eq.) and anhydrous and degazed THF (70 mL) was added, under an argon atmosphere and at 10° C., ketone tert-butyl 5-methoxy-3-(2-(pyridin-3-yl)acetyl)-1H-indol-1-carboxylate (1.2 g, 3.3 mmol, 1.0 eq.). The reaction mixture was stirred at 10° C. for 15 minutes and then, cooled to 0° C. and quenched with a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic layer was dried over MgSO4 and evaporated under reduced pressure. To the alcohol residue taken up in toluene (70 mL) was added KHSO4 (1.1 g, 8.2 mmol) and the mixture was heated at 70° C. for 18 hours and quenched with a saturated aqueous sodium bicarbonate solution, after cooling to room temperature. The mixture was extracted with ethyl acetate and the organic layer was dried over MgSO4 and evaporated. The residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1 to 97/3) to afford the two diastereoisomers represented herein only by the compound (59), namely the major one (E), as a yellow mering (200 mg, 56%, E/Z ratio: 80/20). TLC: Rf=0.30 (CH2Cl2/EtOH, 96/4); IR νmax (cm−1): 2925 (νC—H aliphatic); 1H RMN (DMSO, 500 MHz) δ isomere E (ppm): 2.29 (3H, s, 3H3′), 3.80 (3H, s, 5-methoxy), 6.82 (1H, dd, J6-7=8.9 Hz, J6-4=2.3 Hz, H6), 6.93 (1H, s, H1′), 7.33 (1H, d, J7-6=8.9 Hz, H7), 7.39 (2H, m, H4 et H5″), 7.59 (1H, s, H2), 7.82 (1H, d, J4″-5″=7.9 Hz, H4″), 8.40 (1H, d, J6″-5″=4.6 Hz, H6″), 8.63 (1H, s, H2″), 11.21 (1H, s, indolic H); 13C NMR (DMSO, 75.5 MHz) 8 isomere E (ppm): 18.5 (C3′), 55.9 (5-methoxy), 103.0 (C4), 111.8 (C6), 113.1 (C7), 118.1 (C3), 119.2 (C1′), 123.7 (C5″), 125.3 (C3a), 126.1 (C2), 132.7 (C7a), 134.8 (C3″), 135.1 (C2′), 136.2 (C4″), 146.8 (C6″), 150.4 (C2″), 154.4 (C5); ESI-MS: m/z 265.2 ([M+H]+); HRESI-MS: m/z 265.1340 (calcd for C17H17N2O+, 265.1341).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with a saturated aqueous ammonium chloride solution
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over MgSO4
  5. customevaporated under reduced pressure
  6. temperaturethe mixture was heated at 70° C. for 18 hours
  7. customquenched with a saturated aqueous sodium bicarbonate solution
  8. temperatureafter cooling to room temperature
  9. extractionThe mixture was extracted with ethyl acetate
  10. dry with materialthe organic layer was dried over MgSO4
  11. customevaporated
  12. customThe residue was purified by silica gel flash-column chromatography (eluent: CH2Cl2/EtOH, 99/1 to 97/3)
  13. customto afford the two diastereoisomers

Sources & evidence

ORD record
ord-1cdc0a5ebc044a65bc29c4da4ef3fe9e
Source dataset
uspto-grants-2015_12
Patent number
US09212138B2

Reaction notes

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