Isobutyl chloroformate → HCID 131713869, compound

HRID 1632414Notes

Reaction equation

HRID 1632414 reaction equation
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[CH2:3][C:4](=[O:6])[NH2:5].ClC(OCC(C)C)=O.[NH2:28][C@H:29]([C:34]([NH:36][C@H:37]([C:43]([NH:45][NH:46][C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[O:44])[CH2:38][CH2:39][C:40](=[O:42])[NH2:41])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32]>CN(C)C=O.O1CCCC1.CN1CCOCC1.O>[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([NH:28][C@H:29]([C:34]([NH:36][C@H:37]([C:43]([NH:45][NH:46][C:47]([O:49][C:50]([CH3:52])([CH3:51])[CH3:53])=[O:48])=[O:44])[CH2:38][CH2:39][C:40](=[O:42])[NH2:41])=[O:35])[CH2:30][CH:31]([CH3:33])[CH3:32])=[O:9])[CH2:3][C:4](=[O:6])[NH2:5]

Participants

8

Reactant 3

HCID 62365Isobutyl chloroformate2×HCID 75314Benzyloxycarbonyl-asparagineHCID 131713868HCID 131713868, compound

Product 1

HCID 131713869HCID 131713869, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 79724-MethylmorpholineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

H-Leu-Gln-NHNHBoc obtained in the above-mentioned step 9(a) was dissolved in 30 ml of dimethylformamide, the solution was cooled under stirring condition. On the other hand, 1.61 g of Z-Asn-OH was dissolved in 30 ml of tetrahydrofuran, to this solution 0.62 ml of N-methylmorpholine was added and was cooled to -15° C., then 0.80 ml of isobutyl chloroformate was added dropwise thereto under stirring condition. 30 Seconds after the addition of isobutyl chloroformate, the dimethylformamide solution of H-Leu-Gln-NHNHBoc as prepared previously was added thereto, the whole mixture was stirred at 0° C. for 5 minutes, next at 40° C. for 1 minute in water bath, further at 15° C. for 30 minutes. From the reaction mixture tetrahydrofuran and dimethylformamide were removed by distillation under a reduced pressure, the residue thus obtained was extracted with ethyl acetate. The extract was washed with 1N-citric acid, a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride in this order, then was dried with anhydrous sodium sulfate, and ethyl acetate was removed by distillation. The oily residue obtained was solidified by adding ethyl ehter, reprecipitated from methanol-ethyl acetate to obtain 2.55 g of the desired product.

Workup

  1. temperaturethe solution was cooled
  2. additionwas added
  3. stirringunder stirring condition
  4. additionwas added
  5. customFrom the reaction mixture tetrahydrofuran and dimethylformamide were removed by distillation under a reduced pressure
  6. customthe residue thus obtained
  7. extractionwas extracted with ethyl acetate
  8. washThe extract was washed with 1N-citric acid
  9. dry with materiala saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride in this order, then was dried with anhydrous sodium sulfate, and ethyl acetate
  10. customwas removed by distillation
  11. customThe oily residue obtained
  12. additionby adding ethyl ehter
  13. customreprecipitated from methanol-ethyl acetate

Sources & evidence

ORD record
ord-e80b6bd333cb4de8ab92de4405299c34
Source dataset
uspto-grants-1984_10
Patent number
US04474754

Reaction notes

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