Methyl chloroformate → Carbonic acid 3-(2,5-dimethyl-phenyl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester methyl ester

HRID 1962361Notes

Reaction equation

HRID 1962361 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]1[C:10](=[O:22])[NH:11][C:12]2([CH2:19][CH2:18][N:17]([O:20][CH3:21])[CH2:16][CH2:15]2)[C:13]=1[OH:14].C(N(C(C)C)C(C)C)C.Cl[C:33]([O:35][CH3:36])=[O:34]>ClC1C=CC=CC=1>[CH3:36][O:35][C:33](=[O:34])[O:14][C:13]1[C:12]2([CH2:19][CH2:18][N:17]([O:20][CH3:21])[CH2:16][CH2:15]2)[NH:11][C:10](=[O:22])[C:9]=1[C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 547422463-(2,5-Dimethyl-phenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one

Product 1

HCID 44603930Carbonic acid 3-(2,5-dimethyl-phenyl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester methyl ester

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent3×

Conditions

Temperature
50 °C

Procedure

To a solution of 200 mg of 3-(2,5-dimethyl-phenyl)-4-hydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one and 0.14 ml of ethyl diisopropyl amine in 2 ml of chlorobenzene was added a solution of 66 mg of methyl chloroformate in 0.5 ml of chlorobenzene at 50° C. After stirring for 1 hour at 50° C., the reaction mixture was cooled to room temperature, diluted with 5 ml of chlorobenzene and washed with cold 5% aqueous sodium hydroxide and water. The organic phase was separated, dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica gel. Yield: 120 mg of carbonic acid 3-(2,5-dimethyl-phenyl)-8-methoxy-2-oxo-1,8-diaza-spiro[4.5]dec-3-en-4-yl ester methyl ester (title compound A1). This material was triturated with ethyl acetate/hexane, filtered and dried to afford a solid, mp: 186-188° C.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. washwashed with cold 5% aqueous sodium hydroxide and water
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica gel
  8. customThis material was triturated with ethyl acetate/hexane
  9. filtrationfiltered
  10. customdried
  11. customto afford a solid, mp: 186-188° C.

Sources & evidence

ORD record
ord-b57516b3cc474a2e9c2572dd222ecfd2
Source dataset
uspto-grants-2013_04
Patent number
US08415369B2

Reaction notes

Loading…