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

HRID 1517623Notes

Reaction equation

HRID 1517623 reaction equation
[Cl:1][C:2]1[S:35][C:5]2[C:6]3([CH2:16][CH2:15][N:14]([CH2:17][C:18]4[C:19]([C:30](OCC)=[O:31])=[N:20][N:21]([C:23]5[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][N:24]=5)[CH:22]=4)[CH2:13][CH2:12]3)[O:7][CH2:8][C:9]([F:11])([F:10])[C:4]=2[CH:3]=1.[BH4-].[Li+]>O1CCCC1.C(O)C>[Cl:1][C:2]1[S:35][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]([CH2:17][C:18]1[C:19]([CH2:30][OH:31])=[N:20][N:21]([C:23]2[C:28]([Cl:29])=[CH:27][CH:26]=[CH:25][N:24]=2)[CH:22]=1)[CH2:15][CH2:16]3

Participants

5

Reactant 2

HCID 4148881Lithium borohydrideHCID 67168527ethyl 4-((2'-chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)methyl)-1-(3-chloro-2-pyridyl)-1H-pyrazole-3-carboxylate

Product 1

HCID 58268633[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-1-(3-chloro-2-pyridyl)pyrazol-3-yl]methanolYield 39%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-((2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-yl)methyl)-1-(3-chloro-2-pyridyl)-1H-pyrazole-3-carboxylate (0.4 g, 0.73 mmol) in tetrahydrofuran (5 mL) and ethanol (5 mL) is added lithium borohydride (1.80 mL, 2.0 M solution in tetrahydrofuran, 3.68 mmol) at 0° C. and stirred at room temperature for 16 h. After completion, the reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (2×25 mL). The combined organic extracts are dried over sodium sulfate and concentrated in vacuo. The crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (97:3) to yield 0.14 g (39%) of the title compound. MS (m/z): 500 (M+1).

Workup

  1. customAfter completion, the reaction mixture was quenched with water (10 mL)
  2. extractionextracted with ethyl acetate (2×25 mL)
  3. dry with materialThe combined organic extracts are dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude mixture is purified by column chromatography over silica gel eluting with dichloromethane/methanol (97:3)

Sources & evidence

ORD record
ord-9b5d4741841848f28d4bc2df459bc189
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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