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 1458356Notes

Reaction equation

HRID 1458356 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 (theoretical maximum of 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 CH2Cl2 was stirred under N2 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 956μ (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 CH2Cl2, transferred to a separatory funnel, and shaken with 80 ml of H2O. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. Flash chromatography of the residual gum on silica gel (gradient elution with 0.2-2% MeOH in CH2Cl2) 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 CH2Cl2
  5. customtransferred to a separatory funnel
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customFlash chromatography of the residual gum on silica gel (gradient elution with 0.2-2% MeOH in CH2Cl2) gave 2.81 g (55% overall for Steps 1 and 2) of pale, golden-yellow gum

Sources & evidence

ORD record
ord-cf0ceeb26932446493134dc36e1c78a0
Source dataset
uspto-grants-1998_12
Patent number
US05849764

Reaction notes

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