Hydrochloric Acid → HCID 53863698, compound

HRID 1589592Notes

Reaction equation

HRID 1589592 reaction equation
[CH2:1]([O:8][CH2:9][C@H:10]([C:12]([OH:14])=[O:13])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[Si](C)(C)C.[CH2:20]([O:27][C:28]([NH:30][C@H:31]([C:43](O)=[O:44])[CH:32]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:33]([OH:35])=[O:34])=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[SiH3]OC(=O)[C@@H](COCC1C=CC=CC=1)N.Cl>CN(C)C=O.O1CCCC1.C(Cl)(Cl)Cl>[CH2:20]([O:27][C:28]([NH:30][C@H:31]([C:43]([NH:11][C@@H:10]([C:12]([OH:14])=[O:13])[CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:44])[CH:32]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:33](=[O:34])[OH:35])=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 112114O-Benzyl-D-serineHCID 53769026N-carbobenzoxy-beta-benzyl-L-aspartic acidHCID 123965497O-benzyl-D-serine silyl ester

Product 1

HCID 53863698HCID 53863698, compoundYield 80.4%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

O-Benzyl-D-serine (5.0 g, 25.6 mmole) was dissolved in dimethylformamide (50 ml), treated with chlorotrimethylsilane (3.053 g, 28.1 mmole) and the mixture stirred at room temperature until a homogeneous solution was obtained (approx. 1 hour). Meanwhile, N-benzyloxycarbonyl-β-benzyl-L-aspartic acid (9.14 g, 25.6 mmole) was dissolved in a 1:1 mixture of dimethylformamide and tetrahydrofuran, cooled to -15° C. and treated with N-methylmorpholine (2.81 ml, 25.6 mmole), followed by isobutyl chloroformate (3.32 ml, 25.6 mmole). After 10 minutes' activation, the precooled solution of O-benzyl-D-serine silyl ester was added, followed by dropwise addition of N-methylmorpholine (2.81 ml, 25.6 mmole), ensuring that the temperature of the reaction mixture was maintained at -15° C. The solution was allowed to warm to room temperature slowly and stirred for 4 hours before acidifying to pH 1-2 (with cooling) using aqueous hydrochloric acid. Chloroform was added, the phases separated and the aqueous layer re-extracted with chloroform. The combined organic extracts were washed with 1N hydrochloric acid (3×) and with saturated sodium chloride and dried (MgSO4) The solvent was evaporated under reduced pressure and the solid residue crystallized from ethyl acetate/hexanes to give Nα -benzyloxycarbonyl-β-benzyl-L-aspartyl-O-benzyl-D-serine (11.0 g), m.p. 107°-108° C., which was homogeneous by TLC. The nmr spectrum of the product was consistent with the assigned structure.

Workup

  1. customwas obtained (approx. 1 hour)
  2. temperaturecooled to -15° C.
  3. temperaturewas maintained at -15° C
  4. temperatureto warm to room temperature slowly
  5. stirringstirred for 4 hours
  6. temperaturebefore acidifying to pH 1-2 (with cooling)
  7. customthe phases separated
  8. extractionthe aqueous layer re-extracted with chloroform
  9. washThe combined organic extracts were washed with 1N hydrochloric acid (3×) and with saturated sodium chloride
  10. dry with materialdried (MgSO4) The solvent
  11. customwas evaporated under reduced pressure
  12. customthe solid residue crystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-dfe7d14ec9d44759a789557a853a3c0a
Source dataset
uspto-grants-1986_02
Patent number
US04571345

Reaction notes

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