Diethyl Ether → Ethyl 1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxylate

HRID 1518116Notes

Reaction equation

HRID 1518116 reaction equation
[CH3:1][CH2:2][O:3][CH2:4][CH3:5].[CH3:6][CH2:7]N(C(C)C)C(C)C.Cl[C:16](=[N:22][OH:23])[C:17]([O:19][CH2:20][CH3:21])=[O:18]>C(Cl)Cl>[O:23]1[C:7]2([CH2:5][CH2:4][O:3][CH2:2][CH2:1]2)[CH2:6][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:22]1

Participants

5

Reactant 3

HCID 3283Diethyl Ether2×HCID 81531DiisopropylethylamineHCID 6816376Ethyl chloro(hydroximino)acetate

Product 1

HCID 50994112Ethyl 1,8-dioxa-2-azaspiro[4.5]dec-2-ene-3-carboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The ether solution was transferred to a 100 mL round-bottom flask equipped with a magnetic stir bar, and DIPEA (1.1 eq., 0.96 mL, 5.5 mmol) was added via syringe. Ethyl 2-chloro-2-(hydroxyimino)acetate (1 eq., 758 mg, 5.00 mmol) was dissolved in DCM (50 mL) and placed in a dropping funnel. The DCM solution was added dropwise to the vigorously stirred ether reaction mixture over a period of 2 h. The resulting solution was stirred at RT for 3 days. The solvent was removed under reduced pressure, and the residue was purified by column chromatography using a 24-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 2:3, v/v over 30 min, yielding 264 mg (25%) of the desired ester. 1H-NMR (400 MHz, CDCl3) δ: 4.35 (q, J=7.2 Hz, 2H), 3.89 (ddd, J=11.7, 8.6, 3.4 Hz, 2H), 3.63-3.76 (m, 2H), 2.99 (s, 2H), 1.87-1.98 (m, 2H), 1.74-1.87 (m, 2H), 1.37 (t, J=7.2 Hz, 3H).

Workup

  1. customequipped with a magnetic stir bar
  2. customplaced in a dropping funnel
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by column chromatography
  5. washeluting with EtOAc/hexanes, 0:1 to 2:3, v/v over 30 min

Sources & evidence

ORD record
ord-b16ff516bce74e9fa0324436cfabf728
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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