Ethanol → 3-Methyl-3-prop-2-ynyloxymethyl-1-oxa-4-aza-spiro[4.5]decane

HRID 1962874Notes

Reaction equation

HRID 1962874 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH2:14][OH:15])[NH:8][C:7]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[O:6][CH2:5]1.[CH2:16](Br)[C:17]#[CH:18].C(O)C>C1COCC1.C(OCC)C>[CH3:3][C:4]1([CH2:14][O:15][CH2:18][C:17]#[CH:16])[NH:8][C:7]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[O:6][CH2:5]1

Participants

7

Reactant 4

HCID 702EthanolHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 278563(3-Methyl-1-oxa-4-azaspiro[4.5]decan-3-yl)methanol

Product 1

HCID 595654083-Methyl-3-prop-2-ynyloxymethyl-1-oxa-4-aza-spiro[4.5]decane

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (55% in dispersion in oil) (0.636 g) was added portion wise to a solution of (3-methyl-1-oxa-4-aza-spiro[4.5]dec-3-yl)-methanol (2.0 g) in dry THF (30 ml) at 0° C. The reaction mixture was stirred at room temperature for 1 h. Propargyl bromide (0.972 ml) was added dropwise at 0° C. and the resulting mixture was stirred at room temperature for 2.5 h. The reaction mixture was treated with ethanol (4 ml) and diluted with diethyl ether and the mixture was filtered. The filtrate was concentrated in vacuo to providing a crude residue which was purified by column chromatography (hexane/ethyl acetate 1:1) to give 2.33 g of 3-methyl-3-prop-2-ynyloxymethyl-1-oxa-4-aza-spiro[4.5]decane as an orange liquid. 1H NMR (CDCl3) δ ppm: 4.18 (2H, d); 3.82 (1H, d); 3.53 (1H, d); 3.43 (1H, d); 3.38 (1H, d); 2.42 (1H, t); 1.7-1.2 (10H, m); 1.25 (1H, s).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 2.5 h
  2. filtrationthe mixture was filtered
  3. concentrationThe filtrate was concentrated in vacuo
  4. customto providing a crude residue which
  5. customwas purified by column chromatography (hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-9ac805a7f0304a75bebec0420572c058
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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