Triethylamine → [4-Oxo-4-(4-trifluoromethyl-phenyl)but-2-ynyl]-carbamic acid tert-butyl ester

HRID 1914510Notes

Reaction equation

HRID 1914510 reaction equation
[C:1]([NH:8][CH2:9][C:10]#[CH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[F:12][C:13]([F:24])([F:23])[C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1.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>[C:4]([O:3][C:1](=[O:2])[NH:8][CH2:9][C:10]#[C:11][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][C:14]([C:13]([F:12])([F:23])[F:24])=[CH:15][CH:16]=1)([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamate

Product 1

HCID 66832372[4-Oxo-4-(4-trifluoromethyl-phenyl)but-2-ynyl]-carbamic acid tert-butyl esterYield 37.5%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of N-boc-propargylamine (5.0 g, 32.2 mmol) in THF (100 mL) was added 4-trifluoromethylbenzoyl chloride (4.3 mL, 29.3 mmol), PdCl2(PPh3)2 (0.18 g, 0.264 mmol), and CuI (0.17 g, 0.879 mmol). The mixture was allowed to stir for 5 min at rt, at which time freshly distilled triethylamine (5.1 mL, 36.6 mmol) was added. After 30 min the resulting mixture was filtered, concentrated, and purified by flash column chromatography, or FCC, to afford the title compound as a colorless solid (3.6 g, 35%). MS (ESI): mass calcd. for C16H16F3NO3, 327.1; m/z found, 328.2 [M+H]+. 1H NMR (500 MHz, (DMSO) δ 8.26 (d, J=8.04 Hz, 2H), 7.96 (d, J=8.12 Hz, 2H), 7.62-7.54 (m, 1H), 4.14 (d, J=5.53 Hz, 2H), 1.42 (s, 9H).

Workup

  1. additionwas added
  2. filtrationAfter 30 min the resulting mixture was filtered
  3. concentrationconcentrated
  4. custompurified by flash column chromatography, or FCC

Sources & evidence

ORD record
ord-fb89afd1e1e54eb0b2e2d633cc7c3cc9
Source dataset
uspto-grants-2013_12
Patent number
US08614201B2

Reaction notes

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