Sodium triacetoxyborohydride → 2-chloro-1'-[[1-(3-chloro-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]

HRID 1517620Notes

Reaction equation

HRID 1517620 reaction equation
[Cl:1][C:2]1[S:17][C:5]2[C:6]3([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[O:7][CH2:8][C:9]([F:11])([F:10])[C:4]=2[CH:3]=1.[Cl:18][C:19]1[C:20]([N:25]2[CH:29]=[C:28]([CH:30]=O)[C:27]([CH3:32])=[N:26]2)=[N:21][CH:22]=[CH:23][CH:24]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(O)(=O)C.ClCCl>[Cl:1][C:2]1[S:17][C:5]2[C:6]3([O:7][CH2:8][C:9]([F:11])([F:10])[C:4]=2[CH:3]=1)[CH2:12][CH2:13][N:14]([CH2:30][C:28]1[C:27]([CH3:32])=[N:26][N:25]([C:20]2[C:19]([Cl:18])=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:29]=1)[CH2:15][CH2:16]3

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 582685431-(3-Chloro-2-pyridyl)-3-methyl-pyrazole-4-carbaldehydeHCID 582685982'-Chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-[7H]thieno[2,3-c]pyran]

Product 1

HCID 582685742-chloro-1'-[[1-(3-chloro-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]Yield 56.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran] (0.2 g, 0.71 mmol) in 1,2-dichloroethane (5 mL) are added 1-(3-chloro-2-pyridyl)-3-methyl-pyrazole-4-carbaldehyde (0.19 g, 0.86 mmol) and a few drops of acetic acid. The reaction mixture is stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (0.315 g, 1.43 mmol) is added and stirred at room temperature for 14 hours. After completion, the reaction mixture is diluted with dichloromethane and washed with saturated sodium bicarbonate solution and brine. The organic phase is dried over sodium sulfate and concentrated in vacuo. The crude mixture is purified by HPLC to yield 0.195 g (56%) of 2-chloro-1′-[[1-(3-chloro-2-pyridyl)-3-methyl-pyrazol-4-yl]methyl]-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine]. MS (m/z): 485 (M+1).

Workup

  1. stirringstirred at room temperature for 14 hours
  2. washwashed with saturated sodium bicarbonate solution and brine
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude mixture is purified by HPLC

Sources & evidence

ORD record
ord-4649680252194f979012a7a1c5210a16
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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