Hydrochloric Acid → HCID 53968555, compound

HRID 1589593Notes

Reaction equation

HRID 1589593 reaction equation
[NH2:1][C@@H:2]([C:4]([OH:6])=[O:5])[CH3:3].Cl[Si](C)(C)C.[CH:12]1[C:24]2[CH:23]([CH2:25][O:26][C:27]([NH:29][C@H:30]([C:42](O)=[O:43])[CH:31]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32]([OH:34])=[O:33])=[O:28])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[SiH3]OC(=O)[C@@H](C)N.Cl>CN(C)C=O.CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[CH:12]1[C:24]2[CH:23]([CH2:25][O:26][C:27]([NH:29][C@H:30]([C:42]([NH:1][C@@H:2]([C:4]([OH:6])=[O:5])[CH3:3])=[O:43])[CH:31]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32](=[O:33])[OH:34])=[O:28])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 71080D-AlanineHCID 53993707HCID 53993707, compoundHCID 131714526D-alanine silyl ester

Product 1

HCID 53968555HCID 53968555, compoundYield 87.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

D-Alanine (5 g, 0.056 mole) was dissolved in dimethylformamide (100 ml) and treated with chlorotrimethylsilane (6.7 g, 0.063 mole). The reaction mixture was stirred at room temperature until homogeneous (approx. 1 hour). Meanwhile, Nα -9-fluorenylmethyloxycarbonyl-β-benzyl-L-aspartic acid (22.3 g, 0.050 mole) was dissolved in dimethylformamide/tetrahydrofuran (1:1, v/v, 200 ml), cooled to -15° C. and treated with N-methylmorpholine (5.5 ml, 0.050 mole) and isobutyl chloroformate (6.5 ml, 0.050 mole). After 10 minutes' activation at -15° C., the precooled solution of D-alanine silyl ester from above was added, followed by a second equivalent of N-methylmorpholine (5.5 ml, 0.050 mole). The reaction mixture was allowed to warm to room temperature, stirred for 3 hours and then acidified (pH 1-2) using aqueous hydrochloric acid. The reaction mixture was stirred for 30 minutes and ethyl acetate added and the phases separated. The aqueous phase was re-extracted with ethyl acetate and the combined organic extracts washed with 1N hydrochloric acid (3×) and dried (MgSO4). After evaporation of the solvent under reduced pressure the residue was crystallized from ethyl acetate/hexanes to give Nα -9-fluorenylmethyloxycarbonyl-β-benzyl-L-aspartyl-D-alanine (22.5 g), m.p. 114°-116° C., which was homogeneous by TLC. The nmr spectrum of the product was consistent with the assigned structure.

Workup

  1. temperaturecooled to -15° C.
  2. waitAfter 10 minutes' activation at -15° C.
  3. temperatureto warm to room temperature
  4. stirringstirred for 3 hours
  5. stirringThe reaction mixture was stirred for 30 minutes
  6. customthe phases separated
  7. extractionThe aqueous phase was re-extracted with ethyl acetate
  8. washthe combined organic extracts washed with 1N hydrochloric acid (3×)
  9. dry with materialdried (MgSO4)
  10. customAfter evaporation of the solvent under reduced pressure the residue
  11. customwas crystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-7fdf982638ef491bb29165c165d7a1b9
Source dataset
uspto-grants-1986_02
Patent number
US04571345

Reaction notes

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