Tetrahydrofuran → Ethyl (tert-butoxycarbonyl)-D-methionylglycinate

HRID 1277393Notes

Reaction equation

HRID 1277393 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:2]([C:7]([OH:9])=O)[CH2:3][CH2:4][S:5][CH3:6].C1C2[CH:22]3[C:27](=[O:28])N(O)C(=O)C3C1C=C2.C1CC[CH:33]([N:36]=C=NC2CCCCC2)[CH2:32]C1.C1C[O:48]CC1>>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@@H:2]([C:7]([NH:36][CH2:33][C:32]([O:28][CH2:27][CH3:22])=[O:48])=[O:9])[CH2:3][CH2:4][S:5][CH3:6]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 10868DicyclohexylcarbodiimideHCID 895293a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dioneHCID 111051N-(tert-Butyloxycarbonyl)-D-methionine

Product 1

HCID 12919642Ethyl (tert-butoxycarbonyl)-D-methionylglycinate

Conditions

Temperature
0 °C

Procedure

In 100 ml of THF are dissolved 10.0 g of BOC-(D)-Met-OH and 7.9 g of HONB, followed by cooling at 0° C. and adding 9.0 g of DCC, and the mixture is stirred at 0° C. for 6 hours. Insoluble matters are filtered out, and 5.9 g of H-Gly-OEt·HCl salt and 5.6 ml of TEA are added to the filtrate, which is then stirred overnight at room temperature. The THF is distilled off and the residue is extracted with 100 ml of AcOEt, followed by washing with water and drying over anhydrous sodium sulphate. The AcOEt is distilled off and the residue is crystallized with petroleum ether. Recrystallization from AcOEt-petroleum ether yields 9.8 g of the desired product, m.p. 55°-56° C., Rf1 =0.70, [α]D21 +2.5° (c=0.67, DMF)

Workup

  1. filtrationInsoluble matters are filtered out
  2. addition5.9 g of H-Gly-OEt·HCl salt and 5.6 ml of TEA are added to the filtrate, which
  3. stirringis then stirred overnight at room temperature
  4. distillationThe THF is distilled off
  5. extractionthe residue is extracted with 100 ml of AcOEt
  6. washby washing with water
  7. dry with materialdrying over anhydrous sodium sulphate
  8. distillationThe AcOEt is distilled off
  9. customthe residue is crystallized with petroleum ether
  10. customRecrystallization from AcOEt-petroleum ether

Sources & evidence

ORD record
ord-71976bd1ebbc4054ac36f74a196b4d1f
Source dataset
uspto-grants-1981_07
Patent number
US04277394

Reaction notes

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