Dichloromethane → N-[(1,3-Dimethylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-(2',6'-Dichlorobenzyloxy)Pentanoic Acid, t-Butyl Ester

HRID 634920Notes

Reaction equation

HRID 634920 reaction equation
CCN=C=NCCCN(C)C.C(Cl)Cl.[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([CH3:25])=[C:17]1[C:26]([NH:28][C@H:29]([C:33]([OH:35])=O)[CH:30]([CH3:32])[CH3:31])=[O:27].[NH2:36][CH:37]([CH:46]([OH:58])[CH2:47][O:48][CH2:49][C:50]1[C:55]([Cl:56])=[CH:54][CH:53]=[CH:52][C:51]=1[Cl:57])[CH2:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>C(OCC)(=O)C.CCCCCC>[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([CH3:25])=[C:17]1[C:26]([NH:28][C@H:29]([C:33]([NH:36][CH:37]([CH:46]([OH:58])[CH2:47][O:48][CH2:49][C:50]1[C:51]([Cl:57])=[CH:52][CH:53]=[CH:54][C:55]=1[Cl:56])[CH2:38][C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])=[O:35])[CH:30]([CH3:31])[CH3:32])=[O:27]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 53637592N-(1,3-Dimethylindole-2-Carbonyl)ValineHCID 699869763-amino-5-(2',6'-dichlorobenzyloxy)-4-hydroxypentanoic Acid T-Butyl Ester

Product 1

HCID 86584002N-[(1,3-Dimethylindole-2-Carbonyl)Valinyl]-3-Amino-4-Hydroxy-5-(2',6'-Dichlorobenzyloxy)Pentanoic Acid, t-Butyl EsterYield 41%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

1-tlydroxybenzotriazole hydrate (153 mg, 1.0 mmol) and EDAC (268 mg, 1.4 mmol) were added to a methylene chloride solution of N-(1,3-dimethylindole-2-carbonyl)valine (288 mg, 1.0 mmol, in 3 mL of methylene chloride). The resultant mixture was stirred for 10 minutes under a nitrogen atmosphere at room temperature. A methylene chloride solution of 3-amino-5-(2′,6′-dichlorobenzyloxy)-4-hydroxypentanoic acid, t-butyl ester (364 mg, 1.0 mmol, in 2 mL of methylene chloride) was added to the reaction mixture and the mixture was first stirred for one hour under a nitrogen atmosphere at 0° C., and then for 16 hours at room temperature. The reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution and the aqueous solution was back-extracted with ethyl acetate. The combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine, dried over sodium sulfate, and concentrated to give crude product (583 mg). The crude product was subjected to flash chromatography on silica gel with ethyl acetate/hexane (2/3) to give the title product as a white solid (260 mg). TLC (ethyl acetate/hexanes 1:1): Rf=0.38.

Workup

  1. waitfor 16 hours at room temperature
  2. customThe reaction mixture was partitioned between ethyl acetate and 5% KHSO4 solution
  3. extractionthe aqueous solution was back-extracted with ethyl acetate
  4. washThe combined ethyl acetate solutions were washed with 5% KHSO4 solution, saturated sodium bicarbonate solution (2×) and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto give crude product (583 mg)

Sources & evidence

ORD record
ord-6949bd3959284ebe88a7016819214ae5
Source dataset
uspto-grants-2001_02
Patent number
US06184244B2

Reaction notes

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