Tetrabutylammonium Fluoride → HCID 58468011, compound

HRID 1879362Notes

Reaction equation

HRID 1879362 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:19][CH2:18][C@@H:17]([O:20][Si](C(C)C)(C(C)C)C(C)C)[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH:10]1[OH:31].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(OCC)(=O)C.CCCCCC>O1CCCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:19][CH2:18][C@@H:17]([OH:20])[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[C@H:10]1[OH:31]

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 21226206Ethyl acetate hexaneHCID 66811195HCID 66811195, compound2×

Product 1

HCID 58468011HCID 58468011, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a 100 mL round-bottom flask was dissolved (9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ol (mixture of intermediates 2 and 3, 224.3 mg, 0.501 mmol) in tetrahydrofuran (4 mL) to give a colorless solution. TBAF (0.752 mL, 0.752 mmol) was added, and the mixture was stirred at room temperature for 2 h. LCMS indicated complete conversion of major component while the minor one did not change. Tetrahydrofuran was removed in vacuo and the residue was partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried with Sodium sulfate, and concentrated to give a tan oil. FCC up to 50% ethyl acetate/hexane afforded intermediate 3 unchanged (38 mg, 17%) as a white crystalline solid, and intermediate 4 (95 mg, 65%) as a colorless oil (solidified upon standing). Intermediate 4 was further crystallized and single crystals were obtained. Its relative stereochemistry was proven by x-ray studies.

Workup

  1. customto give a colorless solution
  2. customTetrahydrofuran was removed in vacuo
  3. customthe residue was partitioned between water and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried with Sodium sulfate
  8. concentrationconcentrated
  9. customto give a tan oil
  10. customIntermediate 4 was further crystallized
  11. customsingle crystals were obtained

Sources & evidence

ORD record
ord-c86f705b47eb4c9bba9339dc8f5f3b56
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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