Ethyl Acetate → BocPro-DTrpOH

HRID 2418576Notes

Reaction equation

HRID 2418576 reaction equation
[N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([O:5]N1C(=O)CCC1=O)=O.[NH2:23][C@@H:24]([C:35]([OH:37])=[O:36])[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[NH:28][CH:27]=1.[OH-].[K+].C(OCC)(=O)C>CN(C)C=O.O>[N:1]1([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([NH:23][C@@H:24]([C:35]([OH:37])=[O:36])[CH2:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[NH:28][CH:27]=1)=[O:5]

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 9060D-TryptophanHCID 14797Potassium HydroxideHCID 8538831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) 2-(2,5-dioxo-1-pyrrolidinyl) ester, (2S)-

Product 1

HCID 131713757BocPro-DTrpOHYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A chilled mixture of BocProOSu (96.1 mmole.) and dimethylformamide (100 ml.) was added with cooling to 0° C. to a solution of HDTrpOH (0.1 mole) and potassium hydroxide (85%, 0.1 mole) in dimethylformamide (150 ml.) and water (25 ml.). The mixture was stirred for one hour at 0° C., allowed to warm to room temperature overnight, and stripped of volatiles. The residue was partitioned between ethyl acetate and aqueous citric acid (5%). Crystals which formed between the layers were collected by filtration and recrystallized from methanol-water. More product was obtained by stripping the ethyl acetate layer of ethyl acetate and recrystallizing the residue from methanol-water. The recrystallizates were combined, affording BocProD-TrpOH in 86% yield (33.1 g., m.r. 210°-213° C.).

Workup

  1. additionwas added
  2. temperatureto warm to room temperature overnight
  3. customThe residue was partitioned between ethyl acetate and aqueous citric acid (5%)
  4. customCrystals which formed between the layers
  5. filtrationwere collected by filtration
  6. customrecrystallized from methanol-water
  7. customMore product was obtained
  8. customrecrystallizing the residue from methanol-water

Sources & evidence

ORD record
ord-3fb8309c9c354afa82168c3488c219f9
Source dataset
uspto-grants-1984_09
Patent number
US04472305

Reaction notes

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