Dichloromethane → Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

HRID 2373713Notes

Reaction equation

HRID 2373713 reaction equation
Br[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1.[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[K+].[K+].ClCCl>O1CCOCC1.O.CCOC(C)=O.CCCCCC>[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 86607182Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

Product 1

HCID 86607183Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetateYield 74.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.200 g, 0.5 mmol) was dissolved in dioxane (3 mL) and 2-chlorophenylboronic acid (0.156 g, 1.0 mmol). K2CO3 (0.207 g, 1.5 mmol) was dissolved in H2O (0.2 mL) and added to the dioxane. The solution was degassed by bubbling argon through the mixture for five minutes. {1,1′-Bis(diphenylphosphino)-ferrocene}dichloropalladium(II) complex with dichloromethane (1:1) (0.012 g, 0.015 mmol) was added and the mixture heated under argon to 70° C. for 3 hours (followed by TLC 15:1 hexane:EtOAc). The solvents were removed and the mixture partitioned between EtOAc and H2O. The EtOAc layer was dried (MgSO4) and absorbed onto silica gel. The product was purified by flash chromatography (20:1 hexane:EtOAc) to yield methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.169 g) as a white solid. mp 57-59° C.; 1H NMR (500 MHz, DMSO-d6) δ: 0.87 (t, 6H, J=7.3 Hz), 1.50 (m, 2H), 1.55 (m, 2H), 3.35 (s, 3H), 3.53 (s, 2H), 3.75 (m, 1H), 7.31 (d, 1H, J=7.2 Hz), 7.43 (m, 3H), 7.59 (m, 3H), 7.96 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8.7 Hz). MS (ES) m/z456.1 ([M+H]+). MS (ES) m/z488.1 ([M+CH3OH+H]+). MS (ES) m/z 911.2 ([2M+H]+). Anal. Calcd for C25H26ClNO3S: C, 65.85; H, 5.75; N, 3.07. Found: C, 65.92; H, 5.96; N, 3.27.

Workup

  1. customThe solution was degassed
  2. customby bubbling argon through the mixture for five minutes
  3. customThe solvents were removed
  4. customthe mixture partitioned between EtOAc and H2O
  5. dry with materialThe EtOAc layer was dried (MgSO4)
  6. customabsorbed onto silica gel
  7. customThe product was purified by flash chromatography (20:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-59ed782f7af540ab9671fa07a0656e0f
Source dataset
uspto-grants-2008_12
Patent number
US07459567B2

Reaction notes

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