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

HRID 1532363Notes

Reaction equation

HRID 1532363 reaction equation
[CH2:1]([O:3][C:4](=[O:38])[C:5]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]1[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([CH3:24])[CH:18]=1)=[C:11]2[CH2:25][CH2:26][NH:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)([CH3:7])[CH3:6])[CH3:2].C(N(CC)C(C)C)(C)C.Cl[C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50].C(Cl)Cl.CO>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:38])[C:5]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]1[CH:18]=[C:19]([CH3:24])[CH:20]=[C:21]([CH3:23])[CH:22]=1)=[C:11]2[CH2:25][CH2:26][N:27]([C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1)([CH3:7])[CH3:6])[CH3:2]

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 21226129Dichloromethane methanolHCID 53691851HCID 53691851, compound

Product 1

HCID 699504712-[3-[2-[benzyloxycarbonyl-[4-(pyridin-3-yl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3.00 g (max. 5.86 mmol) of crude 2-[2-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-3-yl)butylamino]ethyl]-1H-indol-5-yl]-2-methylpropionic acid ethyl ester in 30 mL of dry methylene chloride was stirred under nitrogen with cooling in a dry-ice-acetone bath. To this solution was added by syringe 1.106 mL (820 mg, 6.36 mmol) of N,N-diisopropylethylamine. Then 0.956 mL (1.14 g, 6.36 mmol) of benzyl chloroformate was added dropwise by syringe over 5-10 minutes. After 20 minutes, the solution was removed from the cooling bath and allowed to warm to room temperature. After 2 hours, the solution was diluted with 50 mL of methylene chloride, transferred to a separatory funnel, and shaken with 80 mL of water. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography of the residual gum on silica gel (gradient elution with 0.2-2% methanol in methylene chloride gave 2.81 g (55% overall for Steps 1 and 2) of pale, golden-yellow gum; virtually homogeneous by TLC in 95:5 CH2Cl2-MeOH. 500 MHz 1H NMR (CDCl3) was complex, owing to rotamers, but appeared to be consistent with the assigned structure. Mass spectrum (ESI): m/e=646 (M+H).

Workup

  1. temperaturewith cooling in a dry-ice-acetone bath
  2. customthe solution was removed from the cooling bath
  3. waitAfter 2 hours
  4. additionthe solution was diluted with 50 mL of methylene chloride
  5. customtransferred to a separatory funnel
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washFlash chromatography of the residual gum on silica gel (gradient elution with 0.2-2% methanol in methylene chloride
  10. customgave 2.81 g (55% overall for Steps 1 and 2) of pale, golden-yellow gum

Sources & evidence

ORD record
ord-e1d463a11e564d1d922a5cf0be2c9336
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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