Potassium Fluoride → Dimethyl [2,2'-bithiophene]-5,5'-dicarboxylate

HRID 1364496Notes

Reaction equation

HRID 1364496 reaction equation
I[C:2]1[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][C:3]=1[CH3:11].[CH:12]([C:14]1[S:18][C:17](C2SC(NC(=O)C)=NC=2C)=[CH:16][CH:15]=1)=[O:13].[F-].[K+].CC1(C)C(C)(C)OB([C:39]2[S:43][C:42]([C:44]([O:46][CH3:47])=[O:45])=[CH:41][CH:40]=2)O1.C(NCC1SC(C2SC(N[C:65](=[O:67])C)=NC=2C)=CC=1)C=C>C1(C)C=CC=CC=1.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:8]([NH:7][C:5]1[S:6][C:2]([C:39]2[S:43][C:42]([C:44]([O:46][CH3:47])=[O:45])=[CH:41][CH:40]=2)=[C:3]([CH3:11])[N:4]=1)(=[O:10])[CH3:9].[CH3:65][O:67][C:12]([C:14]1[S:18][C:17]([C:39]2[S:43][C:42]([C:44]([O:46][CH3:47])=[O:45])=[CH:41][CH:40]=2)=[CH:16][CH:15]=1)=[O:13]

Participants

10

Reactant 5

HCID 522689Potassium FluorideHCID 11993393Acetamide, N-[5-(5-formyl-2-thienyl)-4-methyl-2-thiazolyl]-HCID 11993394HCID 11993394, compoundHCID 11993593Methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 57417074N-(5-Iodo-4-methyl-2-thiazolyl)acetamide

Product 2

HCID 4072395Dimethyl [2,2'-bithiophene]-5,5'-dicarboxylateHCID 11993589HCID 11993589, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave tube, N-(5-iodo-4-methyl-1,3-thiazol-2-yl)acetamide, Intermediate 1 (150 mg; 0.53 mmol; 1 eq) and Pd(dppf)Cl2 (19.5 mg; 0.03 mmol; 0.05 eq.) are suspended in Toluene (3 ml). Potassium fluoride (123.6 mg; 2.13 mmol; 4 eq.) is dissolved in MeOH (3 ml) and is added to the first solution. Methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate, Intermediate 2 (213.8 mg; 0.80 mmol; 1.50 eq.) is finally added. The resulting solution is flushed with argon, the tube is closed and heated under microwave action at 120° C. for 10 minutes. The desired product is formed together with [2,2′]-bithiophenyl-5,5′-dicarboxylic acid dimethyl ester, the homocoupling product of methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate. Solvents are evaporated and the crude product is purified by preparative HPLC, affording Compound (16) as white-off solid (180 mg; 57%). 1H NMR (DMSO-d6) δ 2.15 (s, 3H), 2.45 (s, 3H), 3.82 (s, 3H, OCH3), 7.24 (d, J=4.5 Hz, 1H), 7.76 (d, J=4.5 Hz, 1H), 12.31 (s, 1H). M−(ESI): 295.10; M+(ESI): 297.12. HPLC, Rt: 3.21 min (purity: 99.6%).

Workup

  1. additionis added to the first solution
  2. customThe resulting solution is flushed with argon
  3. customthe tube is closed

Sources & evidence

ORD record
ord-28b0b193d38d474eae2e9eedca751d4c
Source dataset
uspto-grants-2011_02
Patent number
US07888379B2

Reaction notes

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