Ethylene Glycol → HCID 58313131, compound

HRID 709362Notes

Reaction equation

HRID 709362 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:19]([CH3:21])[CH3:20])[C:7]([N:9]1[CH2:13][C:12](=[O:14])[CH2:11][C@H:10]1[C:15]([O:17][CH3:18])=[O:16])=[O:8])=[O:4].[CH2:22](O)[CH2:23][OH:24].C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCOC(C)=O>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:19]([CH3:21])[CH3:20])[C:7]([N:9]1[C@H:10]([C:15]([O:17][CH3:18])=[O:16])[CH2:11][C:12]2([O:24][CH2:23][CH2:22][O:14]2)[CH2:13]1)=[O:8])=[O:4]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 58313158methyl (S)-1-((methoxycarbonyl)-L-valyl)-4-oxopyrrolidine-2-carboxylate

Product 1

HCID 58313131HCID 58313131, compoundYield 41.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

In a 50 mL round-bottomed flask, (S)-methyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-4-oxopyrrolidine-2-carboxylate (230 mg, 766 μmol, Eq: 1.00) and ethane-1,2-diol (238 mg, 214 μl, 3.83 mmol, Eq: 5) were combined with toluene (15 ml) to give a colorless solution. p-toluenesulfonic acid monohydrate (29.1 mg, 153 μmol) was added and the reaction mixture was heated to 110° C. with a Dean-Stark apparatus for 20 hr. After cooling, it was diluted with EtOAc (50 ml), washed with NaHCO3 (sat solution, 200 ml), dried and concentrated in vacuo. The crude mixture was purified on a silica gel column (CH2Cl2, 20%, 30%, 40% and 60% EtOAc/CH2Cl2) to afford (S)-methyl 7-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-1,4-dioxa-7-azaspiro[4.4]nonane-8-carboxylate as an oil (110 mg, 41.7%). 1H NMR (400 MHz, CHLOROFORM-d) 6 ppm 0.95 (d, J=6.78 Hz, 8H) 1.05 (d, J=6.78 Hz, 7H) 1.57 (s, 2H) 2.22 (dd, J=13.18, 6.90 Hz, 3H) 2.37 (dd, J=13.05, 8.78 Hz, 2H) 3.62-3.70 (m, 11H) 3.71-3.87 (m, 10H) 3.93-4.03 (m, 11H) 4.25 (d, J=2.76 Hz, 4H) 4.59-4.78 (m, 2H) 5.23-5.51 (m, 2H) 5.26-5.51 (m, 2H)

Workup

  1. customto give a colorless solution
  2. temperatureAfter cooling
  3. washwashed with NaHCO3 (sat solution, 200 ml)
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was purified on a silica gel column (CH2Cl2, 20%, 30%, 40% and 60% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-2ab1a0e3be2442e08f7ac0111c771090
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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