Methyl 5-bromothiophene-2-carboxylate → 5-(3-tert-Butoxycarbonylamino-prop-1-ynyl)-thiophene-2-carboxylic Acid Methyl Ester

HRID 480343

Reaction equation

HRID 480343 reaction equation
[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[CH:10])([CH3:4])([CH3:3])[CH3:2].[CH3:12][O:13][C:14]([C:16]1[S:17][C:18](Br)=[CH:19][CH:20]=1)=[O:15]>C(#N)C.CCOC(C)=O.[Cu]I.C(N(CC)CC)C>[CH3:12][O:13][C:14]([C:16]1[S:17][C:18]([C:10]#[C:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:11])=[CH:19][CH:20]=1)=[O:15]

Participants

7

Reactant 2

HCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 540753395-(3-tert-Butoxycarbonylamino-prop-1-ynyl)-thiophene-2-carboxylic Acid Methyl EsterYield 63,406.199%

Reagents, catalysts & solvents 4

HCID 8471TriethylamineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of prop-2-ynyl-carbamic acid tert-butyl ester (1.67 g, 0.011 mmol), 5-bromo-thiophene-2-carboxylic acid methyl ester (2.50 g, 0.011 mmol), tetrakistriphenylphosphine(0) palladium (0.622 g, 0.0538 mmol), CuI (0.102 g, 0.538 mmol) and triethylamine (1.57 mL, 0.011 mmol) in 50 mL acetonitrile under nitrogen was heated at reflux for 16 h. The reaction was cooled to room temperature, diluted with 75 mL EtOAc, washed with 5.5% HCl, water and brine, dried over MgSO4, filtered and concentrated in vacuo to an oil. The product was purified via flash chromatography (9:1 to 4:1 hexanes:EtOAc) to afford the title compound as an oil (2.06 g). MS 313 (M+18).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. washwashed with 5.5% HCl, water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to an oil
  7. customThe product was purified via flash chromatography (9:1 to 4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-6f54f91d847e41e6b7ab1df117abed0c
Source dataset
uspto-grants-2003_11
Patent number
US06649657B2

Linked notes

Loading…