Water → HCID 86679959, compound

HRID 1915749Notes

Reaction equation

HRID 1915749 reaction equation
[N:1]([CH:4]1[CH2:10][CH2:9][N:8]([C:11](OC(C)(C)C)=O)[CH2:7][C:6]([OH:19])([CH3:18])[CH2:5]1)=[N+:2]=[N-:3].Cl[C:21]1[N:25](C)[N:24]=[CH:23][C:22]=1[N+:27]([O-:29])=[O:28].[F-].[K+].O>C(Cl)Cl.FC(F)(F)C(O)=O.CS(C)=O>[N:1]([CH:4]1[CH2:10][CH2:9][N:8]([C:11]2[N:24]([CH3:23])[N:25]=[CH:21][C:22]=2[N+:27]([O-:29])=[O:28])[CH2:7][C:6]([CH3:18])([OH:19])[CH2:5]1)=[N+:2]=[N-:3]

Participants

8

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 123448365-chloro-1-methyl-4-nitro-1H-pyrazoleHCID 86679958HCID 86679958, compound

Product 1

HCID 86679959HCID 86679959, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
70 °C

Procedure

A solution of tert-butyl 5-azido-3-hydroxy-3-methylazepane-1-carboxylate (0.8 g, 3 mmol) in DCM (15 mL) and trifluoroacetic acid (5 mL) was stirred at room temperature for 1.5 hr and then concentrated under reduced pressure. The residue was dissolved in the minimum volume of DCM, loaded onto an SCX column, washed with DCM and MeOH and eluted with 1 N ammonia in MeOH. The solvent was removed under reduced pressure. To a solution of the residue in anhydrous DMSO (10 mL) was added 5-chloro-1-methyl-4-nitro-1H-pyrazole (574 mg, 3.56 mmol) and potassium fluoride (675 mg, 12.7 mmol). The mixture was heated at 70° C. for 16 hr under nitrogen, then cooled and poured into water (300 mL). The mixture was extracted with EtOAc (3×150 mL) and the combined organic layers were washed with water (100 mL) and brine (50 mL), separated, dried over MgSO4 and concentrated to give a brown gum. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 5-azido-3-methyl-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)azepan-3-ol as a mixture of four diastereoisomers (0.38 g, 47% over 2 steps). 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 4.12-3.90 (m, 1H), 3.85 and 3.74 (2s, 3H), 3.60-3.40 (m, 1H), 3.40-3.30 (m, 1H), 3.25-3.10 (m, 1H), 3.00-2.60 (m, 2H), 2.30-2.10 (m, 2H), 2.00-1.70 (m, 2H), 1.35-1.15 (m, 3H). LCMS (ES+) m/z 296 (M+1).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in the minimum volume of DCM
  3. washwashed with DCM and MeOH
  4. washeluted with 1 N ammonia in MeOH
  5. customThe solvent was removed under reduced pressure
  6. temperaturecooled
  7. extractionThe mixture was extracted with EtOAc (3×150 mL)
  8. washthe combined organic layers were washed with water (100 mL) and brine (50 mL)
  9. customseparated
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customto give a brown gum
  13. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-f2be529d0949495db9f462cf68f49323
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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