Sodium Bicarbonate → HCID 66571642, compound

HRID 529310Notes

Reaction equation

HRID 529310 reaction equation
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:12]2[O:17][CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[NH:14]1[CH2:15][CH2:16][O:17][CH:12]([CH2:11][NH:10][C@@H:8]2[CH2:9][C@H:7]2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:13]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 204431481,4-Dioxane hydrochlorideHCID 86708238HCID 86708238, compound

Product 1

HCID 66571642HCID 66571642, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Chloroform (5 mL) was added to a 200 mL round-bottomed flask containing 1,1-dimethylethyl 2-({[trans-2-phenylcyclopropyl]amino}methyl)-4-morpholinecarboxylate (330 mg, 0.993 mmol) to give a suspension. HCl/1,4-Dioxane (6.20 mL, 24.82 mmol) was added and the mixture stirred 18 hours at room temperature. Upon completion, saturated NaHCO3 was added to the reaction mixture and the mixture was extracted with THF—CHCl3 (2×50 mL). The organics were combined, dried over Na2SO4 and concentrated. The residue was adsorbed onto silica and purified via column chromatography on the ISCO Companion (gradient 0-100% 80:20:2 [CHCl3/MeOH/NH4OH]/CHCl3; 12 g column). The compound was further purified via reverse phase column chromatography on Gilson ((C18 column: 0.1% Formic acid H2O/CH3CN, 95-5%) affording the title compound as an amber oil LC-MS (ES) m/z=233 (M+H)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 1H NMR (400 MHz, DMSO-d6) d 7.22 (t, J=7.58 Hz, 2H), 7.11 (t, J=7.33 Hz, 1H), 7.03 (d, J=8.08 Hz, 2H), 3.63-3.73 (m, 1H), 3.35-3.43 (m, 2H), 2.73-2.81 (m, 1H), 2.52-2.70 (m, 4H), 2.25-2.35 (m, 2H), 2.22 (qd, J=2.40, 4.59 Hz, 1H), 1.76 (ddd, J=2.91, 5.94, 9.09 Hz, 1H), 0.86-1.01 (m, 2H).

Workup

  1. customto give a suspension
  2. extractionthe mixture was extracted with THF—CHCl3 (2×50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified via column chromatography on the ISCO Companion (gradient 0-100% 80:20:2 [CHCl3/MeOH/NH4OH]/CHCl3; 12 g column)
  6. customThe compound was further purified via reverse phase column chromatography on Gilson ((C18 column: 0.1% Formic acid H2O/CH3CN, 95-5%)

Sources & evidence

ORD record
ord-899bbda49bdb4594bbce9cd3a00b307b
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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