Methanol → Ly-2940094

HRID 1517605Notes

Reaction equation

HRID 1517605 reaction equation
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:28][CH2:29][C:30]([F:32])([F:31])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:27])=[N:16][N:17]([C:19]2[C:24]([CH:25]=[O:26])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:9][CH2:8]3.[BH4-].[Na+].CO>ClCCl>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:28][CH2:29][C:30]([F:32])([F:31])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:27])=[N:16][N:17]([C:19]2[C:24]([CH2:25][OH:26])=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:18]=1)[CH2:9][CH2:8]3

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 582685962-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde

Product 1

HCID 52914971Ly-2940094Yield 95.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde (12.50 g, 26.10 mmol) in dichloromethane (125 mL) at 0° C. is added sodium borohydride (0.395 g, 10.44 mmol) and methanol (37.50 mL). The ice bath is removed and the reaction is stirred at room temperature for 30 min. Water (50 mL) is added and the mixture is concentrated to half volume resulting in a white sticky solid precipitate. Dichloromethane (100 mL) is added and the biphasic mixture is separated. The organic layer is washed with water (50 mL), dried over sodium sulfate and concentrated to half volume (around 100 mL). Methyl tert-butyl ether (100 mL) is added and the solution is concentrated to provide a precipitate. The solid is filtered and dried under vacuum to give 12 g of [2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]-1′-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol. MS (m/z): 481 (M+1).

Workup

  1. customThe ice bath is removed
  2. additionWater (50 mL) is added
  3. concentrationthe mixture is concentrated to half volume
  4. customresulting in a white sticky solid precipitate
  5. customthe biphasic mixture is separated
  6. washThe organic layer is washed with water (50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to half volume (around 100 mL)
  9. additionMethyl tert-butyl ether (100 mL) is added
  10. concentrationthe solution is concentrated
  11. customto provide a precipitate
  12. filtrationThe solid is filtered
  13. customdried under vacuum

Sources & evidence

ORD record
ord-89d1e9fc972842fc878c8e3188405b7c
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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