Hydrochloric Acid → HCID 71226398, compound

HRID 2409907Notes

Reaction equation

HRID 2409907 reaction equation
[CH3:1][C@:2]1([NH:17]C(=O)OCC2C=CC=CC=2)[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3]1.I[Si](C)(C)C.Cl>C(Cl)Cl.CO>[CH3:1][C@:2]1([NH2:17])[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 85247Trimethylsilyl iodideHCID 71233195HCID 71233195, compound

Product 1

HCID 71226398HCID 71226398, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-benzyl 3-methyl-1-(4-nitrophenyl)piperidin-3-ylcarbamate (525 mg, 1.421 mmol) in CH2Cl2 (5 ml) cooled at 0° C. was added iodotrimethylsilane (0.290 mL, 2.132 mmol) dropwise. After addition, the orange colored solution was stirred at 0° C. for 15 min, then at rt for 1 hr. The reaction was quenched by addition of 4.3 mmol of HCl (1.1 mL of 4N HCl in dioxane) in MeOH (5 mL). The mixture was concentrated. The dark reddish residue was partitioned between ether and water. The ether phase was extracted with 0.2 N aqueous HCl. The combined acidic aqueous solution was extracted with ether (1×), then basified at 0° C. with 1N aqueous NaOH to pH=10. The aqueous phase was extracted with CH2Cl2 (3×). The combined CH2Cl2 extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated to give the desired product, (S)-3-methyl-1-(4-nitrophenyl)piperidin-3-amine (277 mg, 1.177 mmol, 83% yield) as a dark reddish oil. Anal. Calcd. for C12H17N3O2 m/z 235.2, found: 236.0 (M+H)+; 1H NMR (400 MHz, chloroform-d) δ ppm 8.10 (d, J=9.34 Hz, 2 H), 6.83 (d, J=9.34 Hz, 2 H), 3.62-3.50 (m, 1 H), 3.32 (d, J=12.64 Hz, 1 H), 3.18 (s, 1 H), 3.12 (d, J=13.19 Hz, 1 H), 1.82 (d, J=4.95 Hz, 1 H), 1.75 (s, 1 H), 1.69-1.54 (m, 2 H), 1.18 (s, 3 H).

Workup

  1. additionAfter addition
  2. waitat rt for 1 hr
  3. concentrationThe mixture was concentrated
  4. customThe dark reddish residue was partitioned between ether and water
  5. extractionThe ether phase was extracted with 0.2 N aqueous HCl
  6. extractionThe combined acidic aqueous solution was extracted with ether (1×)
  7. custombasified at 0° C. with 1N aqueous NaOH to pH=10
  8. extractionThe aqueous phase was extracted with CH2Cl2 (3×)
  9. washThe combined CH2Cl2 extracts were washed with saturated aqueous NaCl
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-1f0b6b1b02414619a942db0a221d839a
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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