1,2-Dimethoxyethane → tert-Butyl 4-(furan-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1391510Notes

Reaction equation

HRID 1391510 reaction equation
B(O)O.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH:15]=[C:14](OS(C(F)(F)F)(=O)=O)[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5].[Cl-].[Li+].[C:27]([O-])([O-])=O.[Na+].[Na+].CO[CH2:35][CH2:36][O:37][CH3:38]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:4]([O:8][C:9]([N:11]1[CH2:16][CH:15]=[C:14]([C:35]2[CH:27]=[CH:38][O:37][CH:36]=2)[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 5

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 53416367tert-Butyl 4-(furan-3-yl)-3,6-dihydropyridine-1(2H)-carboxylateYield 59%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A flask was charged with boronic acid 3 (6.22 g, 55.6 mmol), triflate 2 (55.27 g, 166.8 mmol, 3 eq.), lithium chloride (7.07 g, 166.8 mmol, 3 eq.), aqueous 2N Na2CO3 (56 mL), 1,2-dimethoxyethane (120 mL) and Pd(PPh3)4 (3.21 g, 2.8 mmol, 0.05 eq.). The reaction mixture was heated to reflux under inert atmosphere for 4 h. After cooling to room temperature the reaction mixture was concentrated under reduced pressure. The resulting residue was partitioned between dichloromethane (150 mL), aqueous 2N Na2CO3 (125 mL), and concentrated ammonium hydroxide (9 mL). The layers were separated and the aqueous layer extracted again with dichloromethane (3×125 mL). The combined organics were dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified via flash column chromatography (hexanes/CH2Cl2/EtOAc 9:1:1) to yield 4 as a light yellow oil (8.13 g, 59%). TLC Rf=0.43; 400 MHz 1H-NMR (CDCl3) δ 1.48 (s, 9H), 2.37 (s, 2H), 3.60 (t, J=3.6 Hz, 2H), 4.03 (s, 2H), 5.87 (s, 1H), 6.51 (s, 1H), 7.38 (d, J=6.8 Hz, 2H); 125 MHz 13C-NMR (CDCl3) δ 26.9, 39.5 (broad), 40.8 (broad), 43.6 (broad), 79.7, 107.2, 118.7 (broad), 126.8, 138.1, 143.5, 154.9. HRMS Calcd. for C14H19NO3Na [M++Na]: 272.1263. Found: 272.1271.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under inert atmosphere for 4 h
  3. concentrationwas concentrated under reduced pressure
  4. customThe resulting residue was partitioned between dichloromethane (150 mL), aqueous 2N Na2CO3 (125 mL), and concentrated ammonium hydroxide (9 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted again with dichloromethane (3×125 mL)
  7. dry with materialThe combined organics were dried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified via flash column chromatography (hexanes/CH2Cl2/EtOAc 9:1:1)

Sources & evidence

ORD record
ord-08293bb2ea2448e7b4260bf297d84177
Source dataset
uspto-grants-2008_03
Patent number
US07338965B2

Reaction notes

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