Tetrabutylammonium Fluoride → (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

HRID 1879368Notes

Reaction equation

HRID 1879368 reaction equation
[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:8]([O:15][Si](C(C)C)(C(C)C)C(C)C)[CH2:7][CH2:6][C@H:5]1[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[F:33])=[N+:2]=[N-:3].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[N:1]([C@@H:4]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C@H:8]([OH:15])[CH2:7][CH2:6][C@H:5]1[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[F:33])=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 71533837(5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

Product 1

HCID 58467993(5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 100 mL round-bottom flask was dissolved (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine (0.732 g, 1.549 mmol) (crude) in tetrahydrofuran (8 mL) to give a colorless solution. TBAF (1.859 mL, 1.859 mmol) was added, and the resulting light yellow solution was stirred at room temperature for 1.5 h. LCMS indicated complete conversion. Tetrahydrofuran was removed and the residue was diluted with water and ethyl acetate. The layers were separated. The organic layer was washed with brine, dried, and concentrated to give a light yellow oil. Purification by FCC up to 60% ethyl acetate/hexane afforded the desired product (crude weight: 480 mg) as a colorless oil. Smaller scale purification afforded an analytical sample: MS(ESI)[M+H+]=317.22; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.51 (dd, J=4.91, 1.38 Hz, 1H) 7.99 (d, J=7.30 Hz, 1H) 7.35 (dd, J=7.81, 5.04 Hz, 1H) 7.06-7.20 (m, 2H) 6.94-7.05 (m, 1H) 5.91 (br. s., 1H) 5.03 (d, J=10.32 Hz, 1H) 4.92 (dd, J=11.21, 2.39 Hz, 1H) 2.84-3.02 (m, 1H) 2.37-2.49 (m, 1H) 2.25-2.36 (m, 1H) 2.07-2.17 (m, J=14.38, 4.94, 3.05, 3.05 Hz, 1H) 1.40-1.64 (m, 1H); 13C NMR (101 MHz, CHLOROFORM-d) δ ppm 158.48 (s, 1C) 152.19-149.87 (dd, J=13.10 and 221 Hz, 1C) 149.72-147.42 (dd, J=13.87 and 219 Hz, 1C) 146.16 (s, 3C) 133.67 (s, 2C) 133.23 (s, 1C) 132.66 (d, J=10.79 Hz, 1C) 124.43 (dd, J=6.94, 3.85 Hz, 2C) 123.84 (br. s., 1C) 122.89 (s, 2C) 115.98 (d, J=17.73 Hz, 2C) 70.94 (s, 3C) 65.67 (s, 1C) 45.43 (br. s., 1C) 35.71 (s, 3C) 33.45 (s, 2C); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −137.55-−137.20 (m, 1F) −142.28-−141.89 (m, 1F).

Workup

  1. customto give a colorless solution
  2. customTetrahydrofuran was removed
  3. additionthe residue was diluted with water and ethyl acetate
  4. customThe layers were separated
  5. washThe organic layer was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto give a light yellow oil
  9. customPurification by FCC up to 60% ethyl acetate/hexane

Sources & evidence

ORD record
ord-9a3cff576c2a47078ff9df58edc288df
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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