Hydrochloric Acid → HCID 66628674, compound

HRID 1665893Notes

Reaction equation

HRID 1665893 reaction equation
C(=O)([O-])O.[Na+].[CH2:6]([O:8][C:9]([C@:11]1([F:31])[C@@H:16]2[C@H:12]1[CH2:13][C@@H:14]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C@@:15]2([NH2:20])[C:17]([OH:19])=[O:18])=[O:10])[CH3:7].Cl[C:33]([O:35][CH2:36][CH:37]=[CH2:38])=[O:34].Cl>O1CCOCC1.O>[CH2:6]([O:8][C:9]([C@:11]1([F:31])[C@@H:16]2[C@H:12]1[CH2:13][C@@H:14]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C@@:15]2([NH:20][C:33]([O:35][CH2:36][CH:37]=[CH2:38])=[O:34])[C:17]([O:19][CH:11]([CH2:12][CH3:13])[CH3:9])=[O:18])=[O:10])[CH3:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 18052Allyl chloroformateHCID 516892Sodium BicarbonateHCID 66628397HCID 66628397, compound

Product 1

HCID 66628674HCID 66628674, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

2 mL of saturated sodium hydrogen carbonate was added to 200 mg of (1R,2R,3R,5R,6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-ethyl ester suspended in 1 mL of dioxane, and the mixture was stirred for 10 minutes at room temperature. 0.18 mL of allyl chloroformate was added thereto, and the solution was stirred for 8 hours at room temperature. After the reaction solution was acidified with 1 mL of 1N hydrochloric acid, 10 mL of water was added thereto, and the mixture was extracted twice with ethyl acetate. The ethyl acetate layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the obtained residue was dissolved in 20 mL of N,N-dimethylformamide. 141 mg of 1-iodobutane and 106 mg of potassium carbonate were added to the solution, and the mixture was stirred for 16 hours at room temperature. Water was added thereto, and the reaction solution was extracted twice with ethyl acetate. After the ethyl acetate layers were combined and dried over anhydrous sodium sulfate, the solvent was distilled under reduced pressure and purified by column chromatography (silica gel: Kanto Chemical silica gel 60 (spherical), eluent: hexane-ethyl acetate=5:1), thereby yielding 159 mg of (1R,2R,3R,5R,6R)-2-allyloxycarbonylamino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-butyl ester 6-ethyl ester.

Workup

  1. stirringthe solution was stirred for 8 hours at room temperature
  2. additionwas added
  3. extractionthe mixture was extracted twice with ethyl acetate
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionthe obtained residue was dissolved in 20 mL of N,N-dimethylformamide
  7. addition141 mg of 1-iodobutane and 106 mg of potassium carbonate were added to the solution
  8. stirringthe mixture was stirred for 16 hours at room temperature
  9. additionWater was added
  10. extractionthe reaction solution was extracted twice with ethyl acetate
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationthe solvent was distilled under reduced pressure
  13. custompurified by column chromatography (silica gel: Kanto Chemical silica gel 60 (spherical), eluent: hexane-ethyl acetate=5:1)

Sources & evidence

ORD record
ord-77d35dc0388e4d8c857310f89edf52ca
Source dataset
uspto-grants-2011_10
Patent number
US08039647B2

Reaction notes

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