Ammonium Chloride → HCID 25004497, compound

HRID 2196099Notes

Reaction equation

HRID 2196099 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][S: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([CH2:15][CH2:14][S:13][CH2:12][CH2:11]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 59286716HCID 59286716, compound

Product 1

HCID 25004497HCID 25004497, compoundYield 67%

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)-thiopyran]-4-carboxylate (40 mg, 0.14 mmol) and 3,5-dichloro-4-picoline (33 mg, 0.20 mmol) in tetrahydrofuran (1.1 mL) was cooled to 0° C. A 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.41 mL, 0.41 mmol) was added and the reaction mixture was allowed to reach room temperature overnight. Saturated aqueous NH4Cl (20 mL) was added. The aqueous phase was extracted with dichloromethane (3×15 mL). The combined organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure. Standard HPLC purification afforded 2-(3,5-dichloropyridine-4-yl)-1-(7-methoxy-2′,3′,5′,6′-tetrahydro-spiro[1,3-benzodioxole-2,4′-(4H)-thiopyran]-4-yl)ethanone (38 mg, 67%). 13C NMR (DMSO) δ 189.1, 148.2, 147.7, 147.0, 141.3, 134.5, 132.8, 122.0, 119.1, 113.0, 107.9, 56.3, 43.6, 35.9, 25.5.

Workup

  1. extractionThe aqueous phase was extracted with dichloromethane (3×15 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-3becadd69c0f4597bf33f8c21933ec8c
Source dataset
uspto-grants-2012_12
Patent number
US08338431B2

Reaction notes

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