Toluene → [4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazol-3-yl]methanol

HRID 1517617Notes

Reaction equation

HRID 1517617 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:31][CH2:32][C:33]([F:35])([F:34])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([C:26](OCC)=[O:27])=[N:16][N:17]([C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:9][CH2:8]3.[H-].C([Al+]CC(C)C)C(C)C.C1(C)C=CC=CC=1.CCCCCC>O1CCCC1.C(OC)(C)(C)C>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:31][CH2:32][C:33]([F:35])([F:34])[C:4]=2[CH:3]=1)[CH2:8][CH2:9][N:10]([CH2:13][C:14]1[C:15]([CH2:26][OH:27])=[N:16][N:17]([C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:11][CH2:12]3

Participants

7

Reactant 4

HCID 1140TolueneHCID 8058HexaneHCID 21225700DiisobutylaluminumhydrideHCID 58268607ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate

Product 1

HCID 58268640[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazol-3-yl]methanolYield 83.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of ethyl 4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-1-(3-fluoro-2-pyridyl)pyrazole-3-carboxylate (2.6 g, 4.93 mmoles) in Tetrahydrofuran (26.00 mL) under N2 atmosphere and cooled to −10 C, Diisobutylaluminum Hydride 1M in toluene (23.68 mL, 23.68 mmoles) is added slowly dropwise. Then, reaction mixture is stirred at that T 15 min and then, the cold bath is removed and the mixture is warmed to room temperature. Then, H2O (100 mL) is added dropwise at −10° C. The resulting suspension is extracted with EtOAc (2×30 mL). Combined organics are washed with H2O (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated to afford a light brown oil that is dissolved in methyl t-butyl ether (10 mL) and white crystals crystallized. Suspension formed is stirred and hexane (10 mL) is added dropwise while stirring. Solid is filtered to give 2 g of the title compound. MS (m/z): 485 (M+1).

Workup

  1. additionis added slowly dropwise
  2. customThen, reaction mixture
  3. customthe cold bath is removed
  4. additionThen, H2O (100 mL) is added dropwise at −10° C
  5. extractionThe resulting suspension is extracted with EtOAc (2×30 mL)
  6. washCombined organics are washed with H2O (50 mL) and brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customto afford a light brown oil that
  10. customwhite crystals crystallized
  11. customSuspension formed
  12. stirringis stirred
  13. stirringwhile stirring
  14. filtrationSolid is filtered

Sources & evidence

ORD record
ord-25fe0f45c4554764be9ccccfde8c34ae
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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