Triethylamine → 5-(3-Methanesulfonylamino-prop-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 480280

Reaction equation

HRID 480280 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][CH:9]=1)=[O:4].[CH2:11]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[C:12]#[CH:13].CCN(CC)CC>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.CC#N>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:13]#[C:12][CH2:11][NH:14][S:15]([CH3:18])(=[O:17])=[O:16])=[CH:8][CH:9]=1)=[O:4]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 14025440N-(Prop-2-yn-1-yl)methanesulfonamide

Product 1

HCID 537526885-(3-Methanesulfonylamino-prop-1-ynyl)-thiophene-2-carboxylic acid methyl esterYield 50.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of 5-bromo-thiophene-2-carboxylic acid methyl ester (1.66 g, 8.0 mmol), N-prop-2-ynyl-methanesulfonamide (1.09 g, 8.2 mmol), Et3N (1.7 mL, 12.1 mmol), and CH3CN (30 mL) was added Pd(PPh3)4 (462 mg, 0.4 mmol) followed by CuI (76 mg, 0.4 mmol). The reaction was heated at reflux for 24 h and was cooled to room temperature. The volatiles were removed in vacuo and the residue was purified via flash chromatography (20% EtOAc in hexanes to 33% EtOAc in hexanes) to yield 5-(3-methanesulfonylamino-prop-1-ynyl)-thiophene-2-carboxylic acid methyl ester as a pale yellow solid (1.1 g). 1H NMR (300 MHz, CDCl3) δ 7.64 (d, 1H), 7.14 (d, 1H), 4.60 (m, 1H), 4.22 (d, 2H), 3.88 (s, 3H), 3.10 (s, 3H); MS 274 (M+1).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. customThe volatiles were removed in vacuo
  4. customthe residue was purified via flash chromatography (20% EtOAc in hexanes to 33% EtOAc in hexanes)

Sources & evidence

ORD record
ord-748b89c385eb487ba195abd096babfd2
Source dataset
uspto-grants-2003_11
Patent number
US06649657B2

Linked notes

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