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1-(Prop-2-yn-1-yl)piperidine → (4-{3-[3-Bromo-5-(3-piperidin-1-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester

HRID 548554
Notes
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Reaction equation

HRID 548554 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1)[C:2]#[CH:3].[CH3:10][O:11][C:12](=[O:34])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[C:24][C:25]2[CH:30]=[C:29]([Br:31])[CH:28]=[C:27](Br)[CH:26]=2)=[CH:17][C:16]=1[CH3:33]>CN(C=O)C.C(N(CC)CC)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[CH3:10][O:11][C:12](=[O:34])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[C:24][C:25]2[CH:26]=[C:27]([C:3]#[C:2][CH2:1][N:4]3[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]3)[CH:28]=[C:29]([Br:31])[CH:30]=2)=[CH:17][C:16]=1[CH3:33]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 2

HCID 3366521-(Prop-2-yn-1-yl)piperidineHCID 67157962{4-[3-(3,5-Dibromo-phenyl)-prop-2-ynyloxy]-2-methyl-phenoxy}-acetic acid methyl ester2×

Product 1

HCID 67157959(4-{3-[3-Bromo-5-(3-piperidin-1-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
Catalyst
HCID 178418397HCID 178418397, compoundCatalyst
HCID 6228DimethylformamideSolvent
HCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-prop-2-ynyl-piperidine (53 mg, 0.44 mmol), {4-[3-(3,5-dibromo-phenyl)-prop-2-ynyloxy]-2-methyl-phenoxy}-acetic acid methyl ester (204 mg, 0.44 mmol, intermediate 2), Pd(PPh3)4 (50 mg, 0.044 mmol), CuI (23 mg, 0.12 mmol) in dry DMF (2 ml) and triethylamine (2 ml) was heated in a microwave own for 30 min at 60° C. in a sealed tube. The reaction mixture was filtered through Decalite and the filtrate was evaporated. The residue was purified on column chromatography using ethyl acetate/methanol mixtures to give (4-{3-[3-bromo-5-(3-piperidin-1-yl-prop-1-ynyl)-phenyl]-prop-2-ynyloxy}-2-methyl-phenoxy)-acetic acid methyl ester in 105 mg (47%) yield.

Workup

  1. filtrationThe reaction mixture was filtered through Decalite
  2. customthe filtrate was evaporated
  3. customThe residue was purified on column chromatography

Sources & evidence

ORD record
ord-c133269f32754ccf9df637f82283c00e
Source dataset
uspto-grants-2011_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07943612B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes