Sodium Carbonate → 4-(2-methoxycarbonylthiophen-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester

HRID 41641

Reaction equation

HRID 41641 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1Br)=[O:4].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[Na+].[Na+]>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.C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH:20]=[C:21]([C:9]2[CH:8]=[CH:7][S:6][C:5]=2[C:3]([O:2][CH3:1])=[O:4])[CH2:22][CH2:23]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2740074Methyl 3-bromothiophene-2-carboxylateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 584428134-(2-methoxycarbonylthiophen-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl esterYield 34.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

3-Bromothiophene-2-carboxylic acid methyl ester (1.0 g, 4.5 mmol, 1.0 eq.), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (1.4 g, 4.5 mmol, 1.0 eq.), THF (50 mL) and Na2CO3 (9 mL, 18 mmol, 4.0 eq.) were combined. The mixture was degassed and purged with nitrogen (3×). PdCl2(PPh3)2 (10.1 g, 0.14 mmol, 0.03 eq.) was added, and the mixture was again degassed and purged with nitrogen (3×), then heated at 80° C. overnight. The mixture was then cooled and the layers were separated. The THF layer was diluted with EtOAc (50 mL), washed with saturated aqueous NaCl (20 mL) and dried over Na2SO4. The material was filtered and applied onto a silica gel column and purified by chromatography with PE/EtOAc (20:1˜10:1) to yield 4-(2-methoxycarbonylthiophen-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (0.5 g) as an oil.

Workup

  1. customThe mixture was degassed
  2. custompurged with nitrogen (3×)
  3. customthe mixture was again degassed
  4. custompurged with nitrogen (3×)
  5. temperatureThe mixture was then cooled
  6. customthe layers were separated
  7. additionThe THF layer was diluted with EtOAc (50 mL)
  8. washwashed with saturated aqueous NaCl (20 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationThe material was filtered
  11. custompurified by chromatography with PE/EtOAc (20:1˜10:1)

Sources & evidence

ORD record
ord-f73dfe24c65a4813a0b174b3809e9756
Source dataset
uspto-grants-2013_09
Patent number
US08530663B2

Linked notes

Loading…