Acetic Acid → HCID 9838554, compound

HRID 1975485Notes

Reaction equation

HRID 1975485 reaction equation
C(O[C:5]([NH:7][CH2:8][CH:9]([C:18]1[CH2:24][C@H:23]2[N:20]([C:21](=[O:28])[C@@H:22]2[C@H:25]([OH:27])[CH3:26])[C:19]=1[C:29]([O:31]CC=C)=[O:30])[CH2:10][NH:11]C(OCC=C)=O)=O)C=C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC1(C)CC(=O)CC(=O)C1.C(O)(=O)C>O1CCCC1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[OH:27][C@@H:25]([C@H:22]1[C:21](=[O:28])[N:20]2[C@@H:23]1[CH2:24][C:18]([CH:9]1[CH2:10][N:11]=[CH:5][NH:7][CH2:8]1)=[C:19]2[C:29]([OH:31])=[O:30])[CH3:26]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 11776TriphenylphosphineHCID 31358DimedoneHCID 57160014HCID 57160014, compound

Product 1

HCID 9838554HCID 9838554, compoundYield 22.8%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of 741 mg of allyl (5R,6S)-3-[2-allyloxycarbonylamino-1-(N-allyloxycarbonylaminomethyl)ethyl]-6-[(R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in 9.25 ml of tetrahydrofuran and 3.07 ml of ethanol were added successively 163 mg of triphenylphosphine, 870 mg of dimedone, 0.089 ml of acetic acid and 143 mg of tetrakis(triphenylphosphine)palladium at room temperature under nitrogen. The mixture was stirred at 30° C. for a few minutes, and then stirring was continued at room temperature for 30 minutes. After a pale yellow precipitate was deposited, 2.2 ml of ethyl acetate was added. The precipitate was filtrated and washed with ethyl acetate and dichloromethane under nitrogen, and dissolved in pH 6.86 buffer solution. 399 mg of Benzyl formimidate hydrochloride was added to the solution at 0° C., while the pH was kept at 8.5. After stirring for 1.5 hours at pH 7.0, the reaction mixture was washed five times with 30% tetrahydrofuran in ethyl acetate while the pH was kept at pH 7. Purification was carried out by a column chromatography on "Diaion HP-20" (trademark, made by Mitsubishi Chemical Industries) (eluent: water followed by 2% acetonitrile in water) and silica gel (eluent: 0-30% water in acetonitrile gradiently) successively to give 99 mg of [5R,6S)-6-[(R)-1-hydroxyethyl]-3-[3,4,5,6-tetrahydropyrimidin-5-yl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.

Workup

  1. stirringstirring
  2. filtrationThe precipitate was filtrated
  3. washwashed with ethyl acetate and dichloromethane under nitrogen
  4. dissolutiondissolved in pH 6.86 buffer solution
  5. addition399 mg of Benzyl formimidate hydrochloride was added to the solution at 0° C., while the pH
  6. stirringAfter stirring for 1.5 hours at pH 7.0
  7. washthe reaction mixture was washed five times with 30% tetrahydrofuran in ethyl acetate while the pH
  8. customPurification

Sources & evidence

ORD record
ord-25714fc4a8844768aa0e01ea6805ee16
Source dataset
uspto-grants-1994_02
Patent number
US05286721

Reaction notes

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