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

HRID 1156952Notes

Reaction equation

HRID 1156952 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 sulfate. 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 +12.5° (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 sulfate
  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-0bca650f6b8d44deb938267694ab8697
Source dataset
uspto-grants-1982_06
Patent number
US04337247

Reaction notes

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