Ammonium Chloride → 2-(3,5-Dichloropyridine-4-yl)-1-(7-methoxy-spiro[1,3-benzodioxole-2,4'-piperidine]-4-yl)ethanone

HRID 2196095Notes

Reaction equation

HRID 2196095 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]([O:19]C)=O)=[CH:5][CH:4]=1)[CH2:15][CH2:14][NH: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][NH:13][CH2:14][CH2:15]3)[O:9][C:8]=2[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:19]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 109538273,5-Dichloro-4-methylpyridineHCID 59286713Methyl 7-methoxy-spiro[1,3-benzodioxole-2,4'-piperidine]-4-carboxylate

Product 1

HCID 250048232-(3,5-Dichloropyridine-4-yl)-1-(7-methoxy-spiro[1,3-benzodioxole-2,4'-piperidine]-4-yl)ethanoneYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl 7-methoxy-spiro[1,3-benzodioxole-2,4′-piperidine]-4-carboxylate (75 mg, 0.268 mol) and 3,5-dichloro-4-picoline (65 mg, 0.40 mmol) in tetrahydrofuran (2.5 mL) was cooled to 0° C. A 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.80 mL, 0.80 mmol) was added and the reaction mixture was allowed to reach room temperature overnight. Saturated aqueous NH4Cl (10 mL) was added. The aqueous phase was extracted with dichloromethane (3×10 mL). The combined organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure. Standard HPLC purification afforded compound 105 (58 mg, 53%). 1H NMR (DMSO) δ 8.66 (s, 2H), 7.38-7.36 (m, 1H), 6.83-6.80 (m, 1H), 4.62 (s, 2H), 3.91 (s, 3H), 3.02-2.91 (m, 4H), 2.12-1.93 (m, 4H).

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  2. dry with materialThe combined organic phase was dried over MgSO4
  3. customevaporated to dryness under reduced pressure
  4. customStandard HPLC purification

Sources & evidence

ORD record
ord-81752ef203fb4625a88c93654c7bd881
Source dataset
uspto-grants-2012_12
Patent number
US08338431B2

Reaction notes

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