Water → 6-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyridin-3-amine

HRID 527619Notes

Reaction equation

HRID 527619 reaction equation
[CH3:1][C:2]1[C:7]2[O:8][CH2:9][C:10]3([CH2:12][CH2:11]3)[C:6]=2[C:5]([O:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][N:15]=2)=[CH:4][CH:3]=1.O.[Cl-].[NH4+]>O1CCCC1>[CH3:1][C:2]1[C:7]2[O:8][CH2:9][C:10]3([CH2:12][CH2:11]3)[C:6]=2[C:5]([O:13][C:14]2[N:15]=[CH:16][C:17]([NH2:20])=[CH:18][CH:19]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 679601262-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxy-5-nitro-pyridine2×

Product 1

HCID 679599396-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl)oxypyridin-3-amineYield 85.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-yl)oxy-5-nitro-pyridine (Intermediate 157, 265 mg) in tetrahydrofuran (5 ml)/water (2.5 ml) iron (245 mg, 4.45 mmol) and then ammonium chloride (238 mg, 4.45 mmol) were added and the reaction mixture was stirred overnight at room temperature. The catalyst was filtered off and the residue was diluted with an aqueous saturated solution of NaHCO3 (5 ml) and extracted with ethyl acetate (3×10 ml). The organic layer was dried over sodium sulphate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents affording the title compound (203 mg) as a light yellow solid.

Workup

  1. filtrationThe catalyst was filtered off
  2. additionthe residue was diluted with an aqueous saturated solution of NaHCO3 (5 ml)
  3. extractionextracted with ethyl acetate (3×10 ml)
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 8:2 to cyclohexane/ethyl acetate 1:1 as eluents

Sources & evidence

ORD record
ord-3fdf0392312f4dd2ae1035c6b6ca2759
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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