4-Methylmorpholine → Z-Thr(tBu)-Pro-OtBu

HRID 1076429Notes

Reaction equation

HRID 1076429 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=O)[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH:38]1[CH2:49][CH2:48][CH2:47][C@H:39]1[C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]>O1CCCC1>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([N:38]1[CH2:49][CH2:48][CH2:47][C@H:39]1[C:40]([O:42][C:43]([CH3:45])([CH3:46])[CH3:44])=[O:41])=[O:12])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 6453108L-Proline 1,1-dimethylethyl esterHCID 7018812(2S,3R)-2-(((Benzyloxy)carbonyl)amino)-3-(tert-butoxy)butanoic acid

Product 1

HCID 131710224Z-Thr(tBu)-Pro-OtBu

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 6.3 g of Z-Thr(tBu)-OH and 2.34 ml of N-methylmorpholine in 100 ml of tetrahydrofuran are added at -17°C 3.0 ml of chloroformic acid-isobutylester, the batch stirred for 20 minutes at this temperature, then reacted with 6.7 g of H-Pro-OtBu in 100 ml of tetrahydrofuran. The batch is allowed to stand at room temperature overnight, then filtered, the filtrate evaporated to dryness under vacuum, the residue dissolved in ethyl acetate and extracted several times with dilute aqueous citric acid solution, dilute aqueous sodium carbonate solution, and saturated sodium chloride solution. The resulting oily compound shows in the thin-layer chromatogram on silica gel:

Workup

  1. waitto stand at room temperature overnight
  2. filtrationfiltered
  3. customthe filtrate evaporated to dryness under vacuum
  4. dissolutionthe residue dissolved in ethyl acetate
  5. extractionextracted several times with dilute aqueous citric acid solution, dilute aqueous sodium carbonate solution, and saturated sodium chloride solution

Sources & evidence

ORD record
ord-afa3ea12d93c43abbc427211af557d51
Source dataset
uspto-grants-1976_05
Patent number
US03956260

Reaction notes

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