Ammonium Chloride → 2-(3,5-dichloropyridine-4-yl)-1-(7-methoxy-2',3',5',6'-tetrahydro-spiro[1,3-benzodioxole-2,4'-(4H)-pyran]-4-yl)ethanone

HRID 2196090Notes

Reaction equation

HRID 2196090 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[O:9][C:10]3([O:16][C:7]=2[C:6]([C:17](OC)=[O:18])=[CH:5][CH:4]=1)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3.[Cl:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([Cl:29])[C:27]=1[CH3:28].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH4+].[Cl-]>O1CCCC1>[Cl:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26]([Cl:29])[C:27]=1[CH2:28][C:17]([C:6]1[C:7]2[O:16][C:10]3([CH2:11][CH2:12][O:13][CH2:14][CH2:15]3)[O:9][C:8]=2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:18]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 109538273,5-Dichloro-4-methylpyridineHCID 59286723methyl 7-methoxy-2',3',5',6'-tetrahydro-spiro[1,3-benzodioxole-2,4'-(4H)-pyran]-4-carboxylate

Product 1

HCID 250044922-(3,5-dichloropyridine-4-yl)-1-(7-methoxy-2',3',5',6'-tetrahydro-spiro[1,3-benzodioxole-2,4'-(4H)-pyran]-4-yl)ethanoneYield 72.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 7-methoxy-2′,3′,5′,6′-tetrahydro-spiro[1,3-benzodioxole-2,4′-(4H)-pyran]-4-carboxylate (1.80 g, 6.42 mmol) and 3,5-dichloro-4-picoline (1.46 g, 8.99 mmol) in tetrahydrofuran (33 mL) was cooled to 0° C. A 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (19.3 mL, 19.3 mmol) was added and the reaction mixture was allowed to reach room temperature overnight. Saturated aqueous NH4Cl (70 mL) was added. The aqueous phase was extracted with dichloromethane (3×100 mL). The combined organic phase was washed with water (50 mL), dried over MgSO4 and evaporated to dryness under reduced pressure. Standard silica gel column chromatography followed by recrystallization from isopropanol afforded 2-(3,5-dichloropyridine-4-yl)-1-(7-methoxy-2′,3′,5′,6′-tetrahydro-spiro[1,3-benzodioxole-2,4′-(4H)-pyran]-4-yl)ethanone (1.90 g, 71%). 13C NMR (DMSO) δ 189.1, 148.2, 147.7, 147.0, 141.2, 134.5, 132.8, 122.0, 118.0, 113.0, 107.8, 64.4, 56.3, 43.5, 35.2.

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane (3×100 mL)
  2. washThe combined organic phase was washed with water (50 mL)
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness under reduced pressure
  5. customStandard silica gel column chromatography followed by recrystallization from isopropanol

Sources & evidence

ORD record
ord-5114aa416b8b492889950fb0cede67a4
Source dataset
uspto-grants-2012_12
Patent number
US08338431B2

Reaction notes

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