Citric Acid → HCID 70149639, compound

HRID 1377166Notes

Reaction equation

HRID 1377166 reaction equation
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:33]1[O:43][C:42]2[CH:41]=[CH:40][C:37]([CH2:38]I)=[CH:36][C:35]=2[O:34]1.C(O)(=O)CC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C.O.CN1CCCN(C)C1=O>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:38][C:37]2[CH:40]=[CH:41][C:42]3[O:43][CH2:33][O:34][C:35]=3[CH:36]=2)[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

Participants

10

Reactant 5

HCID 311Citric AcidHCID 1032Propionic AcidHCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 11086556157766-09-1

Product 1

HCID 70149639HCID 70149639, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
-75 °C

Procedure

Under an N2 atmosphere, a solution of 500 mg of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-dihydrofuran-2-(3H)-one [Example 2b)] in 2 ml of abs. THF and 0.33 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone (DMPU) is cooled down to -75° C. and treated, at an internal temperature of below -70° C., with 3.21 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich, Steinheim, FRG), and this mixture is then stirred at -75° C. for 20 min. 429 mg of 3,4-methylenedioxybenzyl iodide in 1 ml of abs. THF are added dropwise to the reaction solution within the space of 10 min using a syringe, during which period the internal temperature is not allowed to exceed -70° C., and this mixture is then thoroughly stirred at -75° C. for 1 h. 0.611 ml of propionic acid are then added to the clear solution, at from -75° C. to -70° C., using a syringe, and this is followed by 0.611 ml of water. During this procedure, the temperature rises to -30° C. After that, the reaction mixture is diluted with 35 ml of ethyl acetate, and the whole is stirred up with 10 ml of 10% citric acid solution for 5 min in the cold (ice/water cooling). The aqueous phase is separated off and the organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution, and once again with saline. The combined aqueous phases are reextracted 2 times with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The title compound is obtained as a brownish oil. Purification is effected by chromatography on silica gel (eluent D). TLC Rf (D)=0.38; FAB-MS (M+H)+ =440.

Workup

  1. customto exceed -70° C.
  2. stirringthis mixture is then thoroughly stirred at -75° C. for 1 h
  3. customrises to -30° C
  4. customThe aqueous phase is separated off
  5. washthe organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution
  6. dry with materialThe combined organic phases are dried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-44b5ebac7da340fbbc94db757f1dddf4
Source dataset
uspto-grants-1997_09
Patent number
US05663200

Reaction notes

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