Ethyl 6-chloronicotinate → Ethyl 6-[(2,2,4,4-tetramethyl-thiochroman-6-yl)ethynyl]nicotinate

HRID 6560Notes

Reaction equation

HRID 6560 reaction equation
[CH3:1][C:2]1([CH3:16])[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:14]#[CH:15])[CH:8]=2)[S:3]1.Cl[C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][N:19]=1>C(N(CC)CC)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][C:2]1([CH3:16])[CH2:11][C:10]([CH3:12])([CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:14]#[C:15][C:18]3[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][N:19]=3)[CH:8]=2)[S:3]1

Participants

5

Reactant 2

HCID 2799611Ethyl 6-chloronicotinate2×HCID 156611292,2,4,4-Tetramethyl-6-ethynylthiochroman2×

Product 1

HCID 15661155Ethyl 6-[(2,2,4,4-tetramethyl-thiochroman-6-yl)ethynyl]nicotinate

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
55 °C

Procedure

A solution of 232 mg (1.01 mmol) of 2,2,4,4-tetramethyl-6-ethynylthiochroman (Compound 3) and 190 mg (1.03 mmol) of ethyl 6-chloro-nicotinate (Compound 98) in 2 ml of triethylamine was placed in a heavy-walled glass tube, degassed, placed under argon and then treated with a powdered mixture of 53 mg (0.28 mmol) of cuprous iodide and 84 mg (0.12 mmol) of bis(triphenylphosphine) palladium (II) chloride. The mixture was degassed again, placed under argon and the tube was sealed. The reaction mixture was heated at 55 degrees C. for 60 h and then cooled to room temperature. The mixture was treated with water and ether and the organic layer was separated. The aqueous layer was extracted with ether. The organic layers were then combined and washed with saturated NaCl solution and then dried (MgSO4). The solvent was removed in vacuo and the resultant residue was purified by flash chromatography (silica; 10% ethyl acetate in hexanes) to give the title compound as a dark yellow oil. PMR (CDCl3): 1.32-1.43 (15H, m), 1.92 (2H, s), 4.38 (2H, q, J~7.1 Hz), 7.28 (1H, dd, J~8.3 Hz, 1.8 Hz), 7.32-7.38 (2H, m), 7.53 (1H, d, J~8.3 Hz), 8.24 (1H, dd, J~8.2 Hz, 2.2 Hz), 9.16 (1H, d, J~2.2 Hz). MS exact mass, m/e 379.1594 (calcd. for C23H25NO2S. 379.1606).

Workup

  1. customdegassed
  2. customThe mixture was degassed again
  3. customthe tube was sealed
  4. temperaturecooled to room temperature
  5. additionThe mixture was treated with water and ether
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was extracted with ether
  8. washwashed with saturated NaCl solution
  9. dry with materialdried (MgSO4)
  10. customThe solvent was removed in vacuo
  11. customthe resultant residue was purified by flash chromatography (silica; 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-df4dd9f6709d4060bb9662c908f9c9e0
Source dataset
uspto-grants-1993_09
Patent number
US05248777

Reaction notes

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