Dimethylformamide → HCID 66747336, compound

HRID 2401908Notes

Reaction equation

HRID 2401908 reaction equation
Br[C:2]1[C:3]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)=[C:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[S:5][C:6]=1[N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[CH3:27][CH:28]([C:30]1[CH:35]=[C:34](C(C)C)[C:33](C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=[C:32](C(C)C)[CH:31]=1)C.C1(C#C)C=CC=CC=1.CN(C=O)C>CCOC(C)=O.O.CC#N.CC#N.Cl[Pd]Cl>[Cl:26][C:21]1[CH:20]=[C:19]([CH:24]=[CH:23][C:22]=1[Cl:25])[CH2:18][C:3]1[C:2]([C:27]#[C:28][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:6]([N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[S:5][C:4]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10821PhenylacetyleneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 66748037HCID 66748037, compound

Product 1

HCID 66747336HCID 66747336, compoundYield 248.4%

Reagents, catalysts & solvents 3

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of ethyl 4-bromo-3-(3,4-dichlorobenzyl)-5-(morpholin-4-yl)thiophene-2-carboxylate (0.125 g, 0.000222 mol), XPhos (0.0172 g, 0.0000362 mol), CsCO3 (0.199 g, 0.000612 mol) and phenylacetylene (0.146 mL, 0.00133 mol) in DMF (1.2 mL, 0.015 mol) was added bis(acetonitrile)palladium(II) chloride (0.00288 g, 0.0000111 mol) and the mixture was heated at 50° C. overnight. The reaction mixture was diluted with EtOAc (30 mL) and water (15 mL), and the layers were separated. The aqueous layer was extracted with EtOAc (2×15 mL). Combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude residue was purified using a dry load on a silica gel column (eluent: 0-30% EtOAc:hexane), affording ethyl 3-(3,4-dichlorobenzyl)-5-(morpholin-4-yl)-4-(phenylethynyl)thiophene-2-carboxylate (45 mg, 40% yield). LCMS: (FA) ES+ 500, 501, 502; 1H NMR (400 MHz, DMSO) δ 7.55-7.51 (m, 2H), 7.43-7.37 (m, 5H), 7.20 (dd, J=8.3, 2.0 Hz, 1H), 4.38 (s, 2H), 4.22 (q, J=7.1 Hz, 2H), 3.79-3.74 (m, 4H), 3.57-3.52 (m, 4H), 1.23 (t, J=7.1 Hz, 3H).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
  3. dry with materialCombined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified

Sources & evidence

ORD record
ord-cd76778f174e43749e4ec4fc235a2c6f
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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