Hydrochloric Acid → HCID 86679956, compound

HRID 1915734Notes

Reaction equation

HRID 1915734 reaction equation
[F:1][CH:2]1[CH2:8][CH:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:6][CH2:5][N:4]([C:19](OC(C)(C)C)=O)[CH2:3]1.Cl.[F-].[K+].Cl[C:30]1[N:34](C)[N:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37]>CO.CS(C)=O.O>[F:1][CH:2]1[CH2:8][CH:7]([O:9][CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)[CH2:6][CH2:5][N:4]([C:19]2[N:33]([CH3:32])[N:34]=[CH:30][C:31]=2[N+:36]([O-:38])=[O:37])[CH2:3]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 522689Potassium FluorideHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 86679957HCID 86679957, compound

Product 1

HCID 86679956HCID 86679956, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of tert-butyl 3-fluoro-5-(4-methoxybenzyloxy)azepane-1-carboxylate (740 mg, 0.21 mmol) in MeOH (5 mL) was added HCl (4 M in 1,4-dioxane, 5.3 mL, 21 mmol) and the solution was stirred at room temperature for 16 hr. The solvents were removed under reduced pressure and the residue was dissolved in MeOH and loaded onto an SCX column. The column was washed with MeOH and eluted with 7 N ammonia in MeOH. The solvents were removed under reduced pressure to afford a yellow oil. To a solution of this oil in dry DMSO (15 mL) was added potassium fluoride (0.32 g, 8.4 mmol) and 5-chloro-1-methyl-4-nitro-1H-pyrazole (372 mg, 2.31 mmol) and the mixture was heated at 65° C. for 16 hr. After cooling to room temperature, the mixture was diluted with water (300 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (3×50 mL) and the solvent was removed under reduced pressure. Purification via silica gel column chromatography (20-100% EtOAc/isohexane) gave 3-fluoro-5-(4-methoxybenzyloxy)-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepane as a yellow oil (300 g, 55% over two steps). 1H NMR (400 MHz, CDCl3) δ 7.33-7.23 (m, 3H), 6.89-6.86 (m, 2H), 4.82-4.66 (m, 2H), 4.49-3.93 (m, 1H), 3.81 (s, 3H), 3.30-2.99 (m, 4H), 2.95-2.74 (m, 4H), 2.35-2.03 (m, 2H), 1.98-1.83 (m, 2H).

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe residue was dissolved in MeOH
  3. washThe column was washed with MeOH
  4. washeluted with 7 N ammonia in MeOH
  5. customThe solvents were removed under reduced pressure
  6. customto afford a yellow oil
  7. temperaturethe mixture was heated at 65° C. for 16 hr
  8. temperatureAfter cooling to room temperature
  9. extractionextracted with EtOAc (2×50 mL)
  10. washThe combined organic layers were washed with water (3×50 mL)
  11. customthe solvent was removed under reduced pressure
  12. customPurification via silica gel column chromatography (20-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-28612228950841eb937b4424babab3a9
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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