Ethyl 2-oxo-4-oxa-8-azaspiro[4.5]decane-8-carboxylate → Ethyl 3-hydroxy-3-(2-phenylethynyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylate

HRID 2040851Notes

Reaction equation

HRID 2040851 reaction equation
[O:1]=[C:2]1[CH2:6][O:5][C:4]2([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:3]1.[C:17]1([C:23]#[C:24][Mg]Br)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1>[OH:1][C:2]1([C:24]#[C:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:3][C:4]2([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]2)[O:5][CH2:6]1

Participants

4

Reactant 2

HCID 10082452Ethyl 2-oxo-4-oxa-8-azaspiro[4.5]decane-8-carboxylateHCID 178419644HCID 178419644, compound

Product 1

HCID 57493817Ethyl 3-hydroxy-3-(2-phenylethynyl)-1-oxa-8-azaspiro[4.5]decane-8-carboxylateYield 87.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 2-oxo-4-oxa-8-azaspiro[4.5]decane-8-carboxylate (Edwin S. C. Wu, Ronald C. Griffith, James T. Loch III, Alex Kover, Robert J. Murray, George B. Mullen, James C. Blosser, Anthony C. Machulskis, Sally A. McCreedy, J. Med. Chem., 1995, 38 (9), pp 1558-1570, 82 mg, 0.362 mmol) in THF (4 mL) was added dropwise a 1M solution of phenylethynylmagnesium bromide in THF (0.724 mL, 0.724 mmol), stirring at r.t. under anhydrous nitrogen atmosphere. The reaction mixture was stirred at r.t. for 4 h, then at 60° C. for 6 h, then it was quenched with a saturated aqueous solution of ammonium chloride, extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulphate and evaporated to dryness in vacuo. The crude was purified by automated flash chromatography (SP1®TM-Biotage; gradient Petroleum Ether-EtOAc from 75:25 to 4:6) affording the title product as yellow solid. Yield: 87.2%.

Workup

  1. stirringThe reaction mixture was stirred at r.t. for 4 h
  2. customit was quenched with a saturated aqueous solution of ammonium chloride
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulphate
  6. customevaporated to dryness in vacuo
  7. customThe crude was purified by automated flash chromatography (SP1®TM-Biotage; gradient Petroleum Ether-EtOAc from 75:25 to 4:6)

Sources & evidence

ORD record
ord-6ac54eb5fe97458d915fec7bffe53092
Source dataset
uspto-grants-2013_11
Patent number
US08580962B2

Reaction notes

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