tert-butyl N-(prop-2-yn-1-yl)carbamate → tert-Butyl (3-(4-chloro-2-(2,6-difluorobenzoyl)phenyl)prop-2-yn-1-yl)carbamate

HRID 1948856Notes

Reaction equation

HRID 1948856 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([C:8]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])=[O:9])[CH:7]=1.[C:19]([O:23][C:24](=[O:29])[NH:25][CH2:26][C:27]#[CH:28])([CH3:22])([CH3:21])[CH3:20]>C(Cl)Cl.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>[C:19]([O:23][C:24](=[O:29])[NH:25][CH2:26][C:27]#[C:28][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=1[C:8](=[O:9])[C:10]1[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=1[F:17])([CH3:22])([CH3:21])[CH3:20]

Participants

5

Reactant 2

HCID 11073648tert-butyl N-(prop-2-yn-1-yl)carbamateHCID 46835488(5-Chloro-2-iodophenyl)(2,6-difluorophenyl)methanone

Product 1

HCID 52911151tert-Butyl (3-(4-chloro-2-(2,6-difluorobenzoyl)phenyl)prop-2-yn-1-yl)carbamate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

(5-Chloro-2-iodo-phenyl)-(2,6-difluoro-phenyl)-methanone (2aa) (5.5 g, 14.5 mmol), prop-2-ynyl-carbamic acid tert-butyl ester (2.5 g, 16 mmol)7 PdCl2(PPh3)2 (0.6 g, 0.9 mmol) and Cu(I)I (0.2 g, 0.9 mmol) were suspended in anhydrous CH2Cl2 (50 mL) and the mixture was sparged with nitrogen for 30 min. Diethylamine (8 mL) was added and the solution was stirred at room temperature for 16 h. The solution was concentrated in vacuo and the resulting residue purified by column chromatography (silica gel, 0 to 15% EtOAc/hexanes) to afford 3aa (3.6 g, 61%) as a white solid, MS m/z=406 (M+H).

Workup

  1. customthe mixture was sparged with nitrogen for 30 min
  2. additionDiethylamine (8 mL) was added
  3. concentrationThe solution was concentrated in vacuo
  4. customthe resulting residue purified by column chromatography (silica gel, 0 to 15% EtOAc/hexanes)
  5. customto afford 3aa (3.6 g, 61%) as a white solid, MS m/z=406 (M+H)

Sources & evidence

ORD record
ord-49280cb0e5d44552be416770e14f8037
Source dataset
uspto-grants-2013_03
Patent number
US08399659B2

Reaction notes

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