Hydrochloric Acid → HCID 89677023, compound

HRID 2278178Notes

Reaction equation

HRID 2278178 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1.Cl>ClCCl>[F:1][C:2]1[CH:21]=[C:20]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:6][CH2:7][NH:8][CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 89676942HCID 89676942, compound

Product 1

HCID 89677023HCID 89677023, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL round-bottom flask, equipped with a magnetic stir bar, was charged with tert-butyl 4-(2-fluoro-4-morpholinobenzyl)piperazine-1-carboxylate (819 mg, 2.16 mmol) and dichloromethane (14 mL). The resulting solution was cooled to 0° C. Hydrochloric acid (3.2 mL, 4 N in dioxane) was added via syringe. The ice bath was removed and the resulting cloudy suspension was allowed to stir at room temperature overnight. After 20 h, the white suspension was transferred to a 250 mL Erlenmeyer flask and stirred with saturated aqueous sodium carbonate (30 mL), water (20 mL) and dichloromethane (30 mL) for 30 min. The layers were separated and the aqueous layer was extracted twice with dicholomethane (30 mL). The organic layers were washed with saturated aqueous sodium bicarbonate (30 mL), combined, dried over sodium sulfate and concentrated. The resulting yellow oil was chromatographed on a 24 g silica column with a gradient (100% dichloromethane to 90% dichloromethane/10% methanol containing 2M ammonia) to provide 4-(3-fluoro-4-(piperazin-1-ylmethyl)phenyl)morpholine as a yellow oil (580 mg, 96%). 1H NMR 400 MHz (CDCl3) δ 7.22 (t, J=8.5 Hz, 1H), 6.65 (d, J=8.5 Hz, 1H), 6.56 (d, J=13 Hz, 1H) 3.90-3.80 (m, 4H), 3.49 (d, J=14.5 Hz, 2H), 3.20-3.10 (m, 4H), 2.92-2.88 (m, 4H), 2.44 (bs, 4H), 1.64 (s, 1H).

Workup

  1. customA 100 mL round-bottom flask, equipped with a magnetic stir bar
  2. customThe ice bath was removed
  3. waitAfter 20 h
  4. stirringstirred with saturated aqueous sodium carbonate (30 mL), water (20 mL) and dichloromethane (30 mL) for 30 min
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted twice with dicholomethane (30 mL)
  7. washThe organic layers were washed with saturated aqueous sodium bicarbonate (30 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe resulting yellow oil was chromatographed on a 24 g silica column with a gradient (100% dichloromethane to 90% dichloromethane/10% methanol containing 2M ammonia)

Sources & evidence

ORD record
ord-68330da359a541468ad297cb2522805d
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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