Diisopropylamine → 5-Chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine

HRID 1785108Notes

Reaction equation

HRID 1785108 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9](I)[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH2:12].[CH2:13]([O:16][CH2:17][CH:18]1[CH2:20][CH2:19]1)[C:14]#[CH:15].C(NC(C)C)(C)C>C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:10]=[C:9]([C:15]#[C:14][CH2:13][O:16][CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH2:12]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 179805275-Chloro-7-iodo-1,3-benzodioxol-4-amineHCID 18446289((Prop-2-yn-1-yloxy)methyl)cyclopropane

Product 1

HCID 688819705-Chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amineYield 90.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

5-Chloro-7-iodo-1,3-benzodioxol-4-amine (1.0 g, 3.36 mmol) and [(prop-2-yn-1-yloxy)methyl]cyclopropane (739 mg, 6.72 mmol) in ethyl acetate (12 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, then treated with bis(triphenylphosphine) palladium(II) dichloride (236 mg, 10 mol %) followed by copper(I) iodide (64 mg, 10 mol %) and diisopropylamine (681 mg, 6.74 mmol). The reaction was allowed to warm to room temperature and stirred for 4 hours and then filtered through Celite. The filtrate was purified by column chromatography on silica using 40% methyl tert-butyl ether in iso-hexane as eluent to give 5-chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine (850 mg, 90%) as a dark orange oil; NMR Spectrum: (CDCl3) 0.25 (m, 2H), 0.56 (m, 2H), 1.08 (m, 1H), 3.40 (d, 2H), 4.03 (s, 2H), 4.40 (s, 2H), 6.00 (s, 2H), 6.88 (s, 1H).

Workup

  1. filtrationfiltered through Celite
  2. customThe filtrate was purified by column chromatography on silica using 40% methyl tert-butyl ether in iso-hexane as eluent

Sources & evidence

ORD record
ord-ff6d403082bb4c9caf5ce5a3e20fbcf0
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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