Diisopropylethylamine → 2-Chloro-4-(4-nitronaphthalen-1-ylthio)pyridine

HRID 571107Notes

Reaction equation

HRID 571107 reaction equation
[SH2:1].[Na].[Cl:3][C:4]1[CH:9]=[C:8](F)[CH:7]=[CH:6][N:5]=1.F[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([N+:22]([O-:24])=[O:23])=[CH:14][CH:13]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.CCOC(C)=O.CO>[Cl:3][C:4]1[CH:9]=[C:8]([S:1][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([N+:22]([O-:24])=[O:23])=[CH:14][CH:13]=2)[CH:7]=[CH:6][N:5]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2617641-Fluoro-4-nitronaphthaleneHCID 27827922-Chloro-4-fluoropyridineHCID 86586439Sodium hydrogen sulphide

Product 1

HCID 866767482-Chloro-4-(4-nitronaphthalen-1-ylthio)pyridineYield 43%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent3×

Procedure

A suspension of sodium hydrogensulfide (1.53 g, 18.6 mmol) in NMP (8.0 mL) was purged with N2, and was added dropwise to a similarly purged solution of 2-chloro-4-fluoropyridine (1.74 g, 13.3 mmol) in NMP (6.0 mL) over 1 hr. The reaction mixture was kept at RT for 1 hr and then treated dropwise with a solution of 1-fluoro-4-nitronaphthalene (3.80 g, 19.9 mmol) and DIPEA (4.6 mL, 27 mmol) in NMP (10 mL) over 5 min. After a further 1 hr at RT MeOH (5.0 mL) was added and the reaction mixture kept at RT for 48 hr. The resulting mixture was diluted with EtOAc (250 mL) and was washed sequentially with 2M aq. NaOH (2×150 mL), saturated aq. NaHCO3 (150 mL), water (150 mL) and brine (2×150 mL) The organic layer was dried and evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, 120 g, EtOAc in isohexane, 10-30%, gradient elution) to afford 2-chloro-4-(4-nitronaphthalen-1-ylthio)pyridine as a yellow oil (1.95 g, 5.66 mmol, 43%); Rt 5.02 min (Method 1 basic); m/z 317 (M+H)+ (ES+).

Workup

  1. customwas purged with N2
  2. waitthe reaction mixture kept at RT for 48 hr
  3. washwas washed sequentially with 2M aq. NaOH (2×150 mL), saturated aq. NaHCO3 (150 mL), water (150 mL) and brine (2×150 mL) The organic layer
  4. customwas dried
  5. customevaporated in vacuo
  6. customthe residue was purified by flash column chromatography (SiO2, 120 g, EtOAc in isohexane, 10-30%, gradient elution)

Sources & evidence

ORD record
ord-0ae7f36d68e44dd1ad426e3f5d399cd3
Source dataset
uspto-grants-2015_05
Patent number
US09024041B2

Reaction notes

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