Water → (R)-2-Aminomethyl-4-Boc-morpholine

HRID 41102Notes

Reaction equation

HRID 41102 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@H:13]1[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.O>C(CN)O>[NH2:3][CH2:12][C@H:13]1[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1

Participants

4

Reactant 2

HCID 962WaterHCID 67173668(R)-tert-butyl 2-((1,3-dioxoisoindolin-2-yl)methyl)morpholine-4-carboxylate

Product 1

HCID 1515269(R)-2-Aminomethyl-4-Boc-morpholineYield 73%

Reagents, catalysts & solvents 1

HCID 700EthanolamineSolvent

Procedure

A solution of (R)-tert-butyl 2-((1,3-dioxoisoindolin-2-yl)methyl)morpholine-4-carboxylate (37.9 g, 0.11 mol) in ethanolamine (250 mL) was stirred at room temperature for 16 hr. Afterward, the mixture was poured into water (500 mL). The aqueous layer was extracted with EtOAc (3×250 mL), and then the combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (100% EtOAc then 0-10% MeOH in CH2Cl2 (with 1% NH4OH)) to provide the title compound (17.2 g, 73%) as an oil. HRMS (ESI) m/z calcd for C10H20N2O3 217.15 [M+H]+. found 217.28. 1H NMR (300 MHz, CDCl3) δ ppm 1.28 (s, 2H), 1.46 (s, 9H), 2.56-2.70 (m, 1H), 2.73-2.76 (m, 2H), 2.85-2.98 (m, 1 H), 3.30-3.39 (m, 1H), 3.52 (td, J=11.61, 2.82 Hz, 1H), 3.78-3.95 (m, 3H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (3×250 mL)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (100% EtOAc

Sources & evidence

ORD record
ord-334ec0832cbd477792a8c1f65e707058
Source dataset
uspto-grants-2013_09
Patent number
US08530467B2

Reaction notes

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