Pyridine, hydrofluoride (1:1) → HCID 59001066, compound

HRID 1594217Notes

Reaction equation

HRID 1594217 reaction equation
[H][H].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH:14]([CH2:20][C:21]([CH3:23])=[CH2:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:12])=[O:11])=[CH:6][CH:5]=1.N1C=CC=CC=1.[FH:30]>C1COCC1>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][CH:14]([CH2:20][C:21]([F:30])([CH3:23])[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:12])=[O:11])=[CH:8][CH:9]=1.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH:14]2[CH2:20][C:21]([CH3:23])([CH3:22])[O:16][C:15]2=[O:17])(=[O:12])=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 64774Pyridine, hydrofluoride (1:1)2×HCID 59432811HCID 59432811, compoundHCID 178418361HCID 178418361, compound

Product 2

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Hydrogen fluorideepyridine (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-y)-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-y)-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-4786fbb095cd4d71b48446fcb8e4012b
Source dataset
uspto-grants-2007_11
Patent number
US07300936B2

Reaction notes

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