Chlorosuccinimide → Tert-butyl 3-(phenylethynyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylate

HRID 2040839Notes

Reaction equation

HRID 2040839 reaction equation
[C:1]1([C:7]#[C:8][CH:9]=[N:10][OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClN1C(=O)CCC1=O.[CH2:20]=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1>CN(C=O)C>[C:1]1([C:7]#[C:8][C:9]2[CH2:20][C:21]3([CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:23][CH2:22]3)[O:11][N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 27568081-Boc-4-MethylenepiperidineHCID 765430553-Phenylprop-2-ynal oxime

Product 1

HCID 57493807Tert-butyl 3-(phenylethynyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-ene-8-carboxylateYield 85.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of Compound 1a (0.35 g, 2.41 mmol) in 3 mL of DMF stirred at r.t. was added N-chlorosuccinimide (0.386 g, 2.89 mmol) and the solution became orange coloured. After 2 h stirring, the solution became yellow and, after additional 2 h stirring, it was cooled to 0° C. and a solution of tert-butyl 4-methylenepiperidine-1-carboxylate (143 mg, 0.73 mmol) in 0.5 mL of DMF was added, followed by a solution of TEA in 0.5 mL of DMF. The cooling bath was removed and the reaction mixture was stirred at r.t. for 2 days. Afterwards, the reaction mixture was diluted with cold water, extracted with EtOAc. The extracts were washed with brine, dried over Na2SO4, evaporated to dryness in vacuo. The crude was purified by automated flash chromatography (SP1®TM-Biotage; gradient Petroleum Ether-EtOAc from 95:5 to 7:3) affording 210 mg of the title product. Yield: 85.5%.

Workup

  1. waitthe solution became yellow and, after additional 2 h
  2. stirringstirring
  3. customThe cooling bath was removed
  4. stirringthe reaction mixture was stirred at r.t. for 2 days
  5. additionAfterwards, the reaction mixture was diluted with cold water
  6. extractionextracted with EtOAc
  7. washThe extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated to dryness in vacuo
  10. customThe crude was purified by automated flash chromatography (SP1®TM-Biotage; gradient Petroleum Ether-EtOAc from 95:5 to 7:3)

Sources & evidence

ORD record
ord-8d7a518a9ec04196b42c09e5b5ee54af
Source dataset
uspto-grants-2013_11
Patent number
US08580962B2

Reaction notes

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