Pyridine → HCID 59001066, compound

HRID 1893850Notes

Reaction equation

HRID 1893850 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][CH:18]([CH2:24][C:25]([CH3:27])=[CH2:26])[C:19]([O:21][CH2:22][CH3:23])=[O:20])(=[O:16])=[O:15])=[CH:10][CH:9]=1.[FH:28]>C1COCC1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([S:14]([NH:17][CH:18]([CH2:24][C:25]([F:28])([CH3:27])[CH3:26])[C:19]([O:21][CH2:22][CH3:23])=[O:20])(=[O:16])=[O:15])=[CH:12][CH:13]=1.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([NH:17][CH:18]2[CH2:24][C:25]([CH3:27])([CH3:26])[O:20][C:19]2=[O:21])(=[O:16])=[O:15])=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 1049Pyridine3×HCID 14917Hydrofluoric Acid2×HCID 59432811HCID 59432811, compound

Product 2

HCID 59001066HCID 59001066, compoundYield 46%HCID 59432819HCID 59432819, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

pyridine (10 mL) was added to a 0° C. solution of ethyl 2-(4-chloro-benzenesulfonylamino)-4-methyl-4-pentenoate (1.0 g, 3.0 mmol) in THF (15 mL). The reaction mixture was allowed to warm to rt. After 5 h, an additional portion (10 mL) of hydrogen fluoride.pyridine was added. The mixture was stirred for 24 h, then a third portion of hydrogen fluoride.pyridine (10 mL) was added. After a total of 53 h, the reaction was quenched with ice chips (20 mL). The crude mixture was poured into ice water (500 mL) and extracted with CH2Cl2 (2×200 mL). The combined organic layers were washed with sat. aq. NaHCO3 (100 mL) and concentrated in vacuo. The crude concentrate was purified using silica gel column chromatography (10:1 to 5:1 gradient, hexanes/EtOAc) to afford 0.395 g (37% yield) of ethyl 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoate and 0.425 g (46% yield) of 4-chloro-N-(5,5-dimethyl-2-oxo-tetrahydro-furan-3-yl)-benzenesulfonamide. Data for ethyl 2-(4-chlorobenzenesulfonylamino)-4-fluoro-4-methyl-pentanoate: LCMS (M+Na)+374.1; 1H NMR (500 MHz, CDCl3) 7.78 (d, 2H, J=8.9), 7.47 (d, 2H, J=8.5), 5.19 (d, 1H, J=7.9), 4.08 (m, 1H), 3.93 (m, 2H), 2.09-1.94 (m, 2H), 1.42 (d, 3H, J=21.6), 1.37 (d, 3H, J=21.6), 1.12 (t, 3H, J=7.0). Data for 4-chloro-N-(5,5-dimethyl-2-oxo-tetrahydro-furan-3-yl)-benzenesulfonamide: LCMS (M+Na)+326.0; 1H NMR (400 MHz, DMSO-d6) 8.41 (d, 1H, J=9.1), 7.86 (d, 2H, J=8.6), 7.67 (d, 2H, J=8.8), 4.57 (m, 1H), 2.22 (dd, 1H, J=12.4, 9.0), 1.72 (t, 1H, J=12.0), 1.33 (s, 3H), 1.31 (s, 3H).

Workup

  1. customAfter a total of 53 h, the reaction was quenched with ice chips (20 mL)
  2. additionThe crude mixture was poured into ice water (500 mL)
  3. extractionextracted with CH2Cl2 (2×200 mL)
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 (100 mL)
  5. concentrationconcentrated in vacuo
  6. concentrationThe crude concentrate
  7. customwas purified

Sources & evidence

ORD record
ord-b59c1968a6c544fdb76e6ea7deae5a08
Source dataset
uspto-grants-2013_08
Patent number
US08513253B2

Reaction notes

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