Hydrochloric Acid → 2-(N-benzyloxycarbonyl-L-prolyl-L-valyl)amino-6-methylbenzoic acid

HRID 1590804Notes

Reaction equation

HRID 1590804 reaction equation
ClC(OCC(C)C)=O.[CH2:9]([O:16][C:17]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([OH:23])=O)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[CH3:34][C:35]1[C:40]([C:41]([OH:43])=[O:42])=[C:39]([NH:44][C:45](=[O:51])[C@H:46]([CH:48]([CH3:50])[CH3:49])[NH2:47])[CH:38]=[CH:37][CH:36]=1.Cl>C(OCC)(=O)C.CN(C)C=O.O1CCCC1>[CH2:9]([O:16][C:17]([N:19]1[CH2:26][CH2:25][CH2:24][C@H:20]1[C:21]([NH:47][C@H:46]([C:45]([NH:44][C:39]1[CH:38]=[CH:37][CH:36]=[C:35]([CH3:34])[C:40]=1[C:41]([OH:43])=[O:42])=[O:51])[CH:48]([CH3:50])[CH3:49])=[O:23])=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 101987Benzyloxycarbonyl-L-prolineHCID 541805686-methyl-2-(L-valylamino)benzoic acid

Product 1

HCID 537310482-(N-benzyloxycarbonyl-L-prolyl-L-valyl)amino-6-methylbenzoic acidYield 73.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Isobutyl chloroformate (0.1 ml) was added dropwise to a tetrahydrofuran solution (2.5 ml) containing N-benzyloxycarbonyl-L-proline (229 mg) and N-methylmorpholine (0.1 ml) at -12° C. to -18° C., and the mixture was stirred at this temperature for nine minutes. An N,N-dimethylformamide solution (1.5 ml) containing 6-methyl-2-(L-valylamino)benzoic acid (142 mg) and N-methylmorpholine (0.075 ml) was added dropwise to the above solution at -15° C., and the resultant solution was stirred at this temperature for 20 minutes and then at room temperature for 45 minutes. Thereafter, 1N hydrochloric acid was added to stop the reaction, and extraction was performed using ethyl acetate. The organic layer was successively washed with 1N hydrochloric acid and brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography using silica gel to obtain 202 mg of 2-(N-benzyloxycarbonyl-L-prolyl-L-valyl)amino-6-methylbenzoic acid.

Workup

  1. additionwas added dropwise to the above solution at -15° C.
  2. waitat room temperature for 45 minutes
  3. customthe reaction, and extraction
  4. washThe organic layer was successively washed with 1N hydrochloric acid and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-8f66ab7ea13f45ce9a92f01169b0ab9f
Source dataset
uspto-grants-1993_04
Patent number
US05204462

Reaction notes

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