Ethylene Glycol → (S)-benzyl 7-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-1,4-dioxa-7-azaspiro[4.4]nonane-8-carboxylate

HRID 1751538Notes

Reaction equation

HRID 1751538 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:25]([CH3:27])[CH3:26])[C:7]([N:9]1[CH2:13][C:12](=[O:14])[CH2:11][C@H:10]1[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])=[O:8])=[O:4].C1(C)C=CC(S(=O)=O)=CC=1.[CH2:38](O)[CH2:39][OH:40]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:25]([CH3:27])[CH3:26])[C:7]([N:9]1[C@H:10]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:11][C:12]2([O:40][CH2:39][CH2:38][O:14]2)[CH2:13]1)=[O:8])=[O:4]

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 59610664(S)-benzyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-oxopyrrolidine-2-carboxylateHCID 178427284HCID 178427284, compound

Product 1

HCID 59611049(S)-benzyl 7-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-1,4-dioxa-7-azaspiro[4.4]nonane-8-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(S)-benzyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-oxopyrrolidine-2-carboxylate (2.45 g, 6.51 mmol) in a round bottom flask was dissolved in anhydrous toluene (200 mL) and p-toluene sulfonic acid monohydride (124 mg, 0.1 mmol) and ethylene glycol (808 mg, 13.02 mmol) were added and the mixture was refluxed for 18 hours, removing the generated byproduct water with a Dean-Stark apparatus. The crude mixture was then diluted with ethyl acetate and washed, respectively, with 10% citric acid, saturated ammonium chloride, 10% sodium carbonate and finally with brine. The organic layers were combined and dried over sodium sulfate and concentrated down on rotovap. The crude residue was then purified on normal phase column chromatography with 5% MeOH/DCM. (2.3 g, 84%)

Workup

  1. temperaturethe mixture was refluxed for 18 hours
  2. customremoving the generated byproduct water with a Dean-Stark apparatus
  3. additionThe crude mixture was then diluted with ethyl acetate
  4. washwashed
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated down on rotovap
  7. customThe crude residue was then purified on normal phase column chromatography with 5% MeOH/DCM

Sources & evidence

ORD record
ord-da302e103e5b470e91f2fa67f7779744
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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