Diethyl Ether → HCID 20212117, compound

HRID 1906517Notes

Reaction equation

HRID 1906517 reaction equation
[OH:1][CH:2]([CH2:15][NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][C:6]=1I.[C:21]1([C:27]#[CH:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOCC>C(N(CC)CC)C.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH2:1].[OH:1][CH:2]([CH2:15][NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH2:11])=[O:10])=[CH:7][C:6]=1[C:28]#[C:27][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 3

HCID 3283Diethyl EtherHCID 10821PhenylacetyleneHCID 13823540HCID 13823540, compound

Product 1

HCID 20212117HCID 20212117, compoundYield 65.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 3.75 g (9.57 mmoles) of 4-(2-hydroxy-3-[(1,1-dimethylethyl)amino]propoxy]-3-iodobenzamide, 1.6 ml (14.35 mmole) of phenylacetylene, 0.036 g (0.048 mmole) of (Ph3P)2PdCl2 and 0.018 g (0.0957 mmole) of copper (I) iodide in 20 ml of triethylamine and 10 ml of THF (which had been deoxygenated by admission of N2) was stirred at 25° C. under N2 for one hour. It was heated at 60° for 3 hr. The precipitate which formed on cooling was collected by filtration and dried in vacuo. A fumarate salt was prepared in MeOH solvent and ether was added. A total of 3.0 g was collected by filtration in two crops. The solid was stirred with dilute NaOH and the crystalline free base was collected by filtration. The solid was recrystallized from CH3CN to give 1.2 g of crystalline 4-[2-hydroxy-3-[(1,1 -dimethylethyl)amino]propoxy]-3-(phenylethynyl)benzamide hydrate (4:1), mp 167°-169° C.

Workup

  1. temperatureIt was heated at 60° for 3 hr
  2. customThe precipitate which formed
  3. temperatureon cooling
  4. filtrationwas collected by filtration
  5. customdried in vacuo
  6. filtrationA total of 3.0 g was collected by filtration in two crops
  7. filtrationthe crystalline free base was collected by filtration
  8. customThe solid was recrystallized from CH3CN

Sources & evidence

ORD record
ord-b15266b2c68f4f3293b837c9336fcc00
Source dataset
uspto-grants-1987_03
Patent number
US04652584

Reaction notes

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