4-Methylmorpholine → 3-[(N-acetylprolyl)alanylprolylamino]-2-hydroxybutanoic acid, methyl ester

HRID 366937Notes

Reaction equation

HRID 366937 reaction equation
[NH:1]1[CH2:20][CH2:19][CH2:18][C@H:2]1[C:3]([NH:5][C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12]([OH:14])=O)=[O:9])[CH3:7])=[O:4].CN1CC[O:25][CH2:24][CH2:23]1.C(OC(Cl)=O)C(C)C.[NH2:36][C@@H:37]([CH3:44])[CH:38]([OH:43])[C:39]([O:41][CH3:42])=[O:40]>C(#N)C.C(Cl)(Cl)Cl>[C:24]([N:1]1[CH2:20][CH2:19][CH2:18][C@H:2]1[C:3]([NH:5][C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12]([NH:36][CH:37]([CH3:44])[CH:38]([OH:43])[C:39]([O:41][CH3:42])=[O:40])=[O:14])=[O:9])[CH3:7])=[O:4])(=[O:25])[CH3:23]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 9817252L-prolyl-L-alanyl-L-prolineHCID 56623301methyl (3S)-3-amino-2-hydroxybutanoate

Product 1

HCID 145033163-[(N-acetylprolyl)alanylprolylamino]-2-hydroxybutanoic acid, methyl esterYield 36.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
-15 °C

Procedure

Ac-L-prolyl-L-alanyl-L-proline (0.65 g, 2.00 mmol) was suspended in dry acetonitrile (20 ml) under an argon atmosphere in a flask fitted with an overhead stirrer and internal thermometer. The suspension was cooled to -15° C. and N-methylmorpholine (0.22 ml, 2.00 mmol) was added followed by isobutylchloroformate (0.26 ml, 2.00 mmol) at such a rate as to maintain the internal reaction temperature at -10° to -15° C. After minutes, a solution of methyl (3S)-3-amino-2-hydroxybutanoate (0.53 g, 4.00 mmol) in chloroform (2.5 ml) was added at such a rate as to maintain the internal reaction temperature at -10° to -15° C. The reaction mixture was slowly warmed to room temperature and then stirred for 3 hours. The reaction mixture was evaporated on a rotary evaporator, the residue dissolved in water (20 ml) and treated with a mixed bed resin (J. T. Baker--ANGMI-615, 11.0 g). After 15 minutes the mixture was filtered and the filtrate evaporated on a rotary evaporator. Chromatography using methylene chloride-methanol as the eluent gave the above-named product (0.32 g) in 36% yield.

Workup

  1. customfitted with an overhead stirrer
  2. temperatureto maintain the internal reaction temperature at -10° to -15° C
  3. waitAfter minutes
  4. temperatureto maintain the internal reaction temperature at -10° to -15° C
  5. temperatureThe reaction mixture was slowly warmed to room temperature
  6. customThe reaction mixture was evaporated on a rotary evaporator
  7. dissolutionthe residue dissolved in water (20 ml)
  8. additiontreated with a mixed bed resin (J. T. Baker--ANGMI-615, 11.0 g)
  9. filtrationAfter 15 minutes the mixture was filtered
  10. customthe filtrate evaporated on a rotary evaporator

Sources & evidence

ORD record
ord-87e955c083404628b4dcce2d5397925c
Source dataset
uspto-grants-2000_10
Patent number
US06130315

Reaction notes

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