Trifluoroacetic acid → HCID 50996345, compound

HRID 1404148Notes

Reaction equation

HRID 1404148 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][CH2:3]1.[CH2:15]([O:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:24]=1[CH:25]=[CH:26][N:27]2[CH2:33][CH3:34])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.FC(F)(F)C(O)=O>C(O)(=O)C>[CH2:15]([O:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]2[C:24]=1[C:25]([C:2]1[CH2:3][CH2:4][NH:5][CH2:6][CH:7]=1)=[CH:26][N:27]2[CH2:33][CH3:34])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 58303952HCID 58303952, compound

Product 1

HCID 50996345HCID 50996345, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

In pressure vessel, tert-butyl 4-oxopiperidine-1-carboxylate (370 mg, 1.86 mmol) was dissolved in acetic acid (3 mL) and then 4-(benzyloxy)-1-ethyl-6-fluoro-1H-indole (200 mg, 0.74 mmol) was added, followed by trifluoroacetic acid (1 mL). The reaction mixture was heated to 80° C. for 1 hour. Volatiles were evaporated and then water was added. The pH was adjusted to ˜12 with 15% aqueous NaOH and partitioned between EtOAc-water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give a crude product. The resulting residue was purified on alumina column chromatography eluting with DCM/methanol (0-6%) to afford 37-3 (84 mg, 32%). 1H NMR (300 MHz, DMSO-d6) δ (ppm) 8.78 (br. s, 2H), 7.51-7.41 (m, 5H), 7.27 (s, 1H), 6.99 (dd, J=9.9 Hz and 2.1 Hz, 1H), 6.63 (dd, J=11.8 Hz and 2.1 Hz, 1H), 5.84, (br. s, 1H), 5.16 (s, 2H), 4.11 (q, J=7.2 Hz, 2H), 3.46 (br. s, 2H), 2.93 (br.s, 2H), 2.61 (br. s, 2H), 1.31 (t, J=7.2 Hz, 3H). LCMS: calc 350.4 and found: 351.1 [MH]+.

Workup

  1. customVolatiles were evaporated
  2. additionwater was added
  3. custompartitioned between EtOAc-water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude product
  9. customThe resulting residue was purified on alumina column chromatography
  10. washeluting with DCM/methanol (0-6%)

Sources & evidence

ORD record
ord-7af07c756bdd475cb279f2a591d0d65a
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

Loading…