4-Methylmorpholine → 3-Benzyloxycarbonylamino-succinamic acid tert-butyl ester

HRID 1814342Notes

Reaction equation

HRID 1814342 reaction equation
[C:1]([O:5][C:6](=[O:23])[CH2:7][C@H:8]([NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C:9](O)=[O:10])([CH3:4])([CH3:3])[CH3:2].C[N:25]1CCOCC1.[OH-].[NH4+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:23])[CH2:7][CH:8]([NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C:9]([NH2:25])=[O:10])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 1110824-tert-Butyl hydrogen N-((phenylmethoxy)carbonyl)-L-aspartate

Product 1

HCID 27287123-Benzyloxycarbonylamino-succinamic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (S)-2-benzyloxycarbonylamino-succinic acid-4-tert-butyl ester (20.0 g, 61.9 mmol) in CH2Cl2 (100 mL) at −10° C. in a salt/ice/water bath was added N-methylmorpholine (8.20 mL, 74.20 mmol). This was followed by dropwise addition of isobutyl chlorofomate (9.63 mL, 74.20 mmol), over 20 min. After 30 min of stirring at −10° C., ammonium hydroxide solution (28% w/w ammonia, 100 mL) was added portionwise over 5 min. The reaction mixture was stirred for another 8 h then followed by removal of the CH2Cl2 in vacuo. The remaining solution was extracted with EtOAc. The combined extracts were washed with 100 mL of each of the following: 5% citric acid, saturated NaHCO3, and brine. Drying and removal of solvents under vacuum gave crude oil which crystallized from Et2O/hexanes mixture. 3-benzyloxycarbonylamino-succinamic acid tert-butyl ester was obtained in 95% yield (19.0 g). MS (APCI) m/z 323.2 (M+1).

Workup

  1. additionThis was followed by dropwise addition of isobutyl chlorofomate (9.63 mL, 74.20 mmol), over 20 min
  2. stirringThe reaction mixture was stirred for another 8 h
  3. customthen followed by removal of the CH2Cl2 in vacuo
  4. extractionThe remaining solution was extracted with EtOAc
  5. washThe combined extracts were washed with 100 mL of each of the following: 5% citric acid, saturated NaHCO3, and brine
  6. customDrying
  7. customremoval of solvents under vacuum
  8. customgave crude oil which
  9. customcrystallized from Et2O/hexanes mixture

Sources & evidence

ORD record
ord-5760ac771da1422bbb4623f74fbd72ee
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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