Benzyl chloroformate → 3-[2-[benzyloxycarbonyl-[4-(pyridin-4-yl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid ethyl ester

HRID 1532358Notes

Reaction equation

HRID 1532358 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:15]1[CH:20]=[C:19]([CH3:21])[CH:18]=[C:17]([CH3:22])[CH:16]=1)=[C:9]2[CH2:23][CH2:24][NH:25][CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1)=[O:5])[CH3:2].C(N(CC)C(C)C)(C)C.Cl[C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:47]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]([C:15]1[CH:16]=[C:17]([CH3:22])[CH:18]=[C:19]([CH3:21])[CH:20]=1)=[C:9]2[CH2:23][CH2:24][N:25]([C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:47])[CH2:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 543970972-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-4-yl)butylamino]-ethyl]-1H-indole-5-carboxylic acid ethyl ester

Product 1

HCID 541035193-[2-[benzyloxycarbonyl-[4-(pyridin-4-yl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3.19 g (6.83 mmol) of 2-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-4-yl)butylamino]ethyl]-1H-indole-5-carboxylic acid ethyl ester in 25 mL of dry methylene chloride was stirred under nitrogen and cooled to −78° C. in a dry ice-acetone bath as 2.38 mL (1.76 g, 13.7 mmol) of N,N-diisopropylethylamine was added, followed by gradual addition of 3.4 mL (4.06 g; 23.7 mmol) of benzyl chloroformate by syringe, in portions. After about 2.5 hours, the solution was removed from the cooling bath and allowed to warm to room temperature. It was then partitioned between ethyl acetate and 5% aqueous potassium bisulfate solution. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (elution with a gradient of 0.5-10% methanol in methylene chloride) afforded a quantitative yield of the product as a yellow foam. 500 MHz 1H NMR was complex, owing to the existence of rotamers, but was consistent with the assigned structure. Mass spectrum (PB-NH3/CI): m/e=604.3 (M+H).

Workup

  1. additionwas added
  2. customthe solution was removed from the cooling bath
  3. customIt was then partitioned between ethyl acetate and 5% aqueous potassium bisulfate solution
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography on silica gel (
  8. washelution with a gradient of 0.5-10% methanol in methylene chloride)

Sources & evidence

ORD record
ord-a42b59595bdc49dc9f0e1ae8709b843d
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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