Dichloromethane → (1H-Indol-7-yl)-carbamic acid benzyl ester

HRID 13698

Reaction equation

HRID 13698 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.C(Cl)Cl.[OH-].[Na+].Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>CCCCCCC>[CH2:20]([O:19][C:17](=[O:18])[NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 1116347-Aminoindole

Product 1

HCID 24749680(1H-Indol-7-yl)-carbamic acid benzyl esterYield 96.7%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Conditions

Temperature
55 °C

Procedure

Equip a 12-L reaction flask with a cooling bath, air driven stirring apparatus, addition funnel, and thermometer probe. Thoroughly purge the flask with nitrogen, charge 7-aminoindole (352 g, 2.663 moles), CH2Cl2 (5.30 L, 15 volumes) and 2N NaOH (1.76 L, 3.515 moles). After cooling the biphasic solution to less than 10° C., benzyl chloroformate (500 g, 2.929 moles) add dropwise at such a rate so as to maintain the temperature at less than 10° C. over one hour. Stir the reaction vigorously for 1 hour until complete by TLC. Separate the layers and extract the aqueous layer with CH2Cl2 (1.7 L). Combine the organic layers, wash with 2N NaOH (2×2 L), and dry over Na2SO4. After filtering off the drying agent, concentrate the filtrate in vacuo to a volume of ˜1.5 L resulting in thin dark mixture. Gradually exchange the solvent using heptane (˜4 L) to form a thick sand-like slurry and increase the bath temperature to 50-60° C. Concentrate to a volume of ˜1.5 L, filter while hot (50-60° C.), wash with warm (45° C.) heptane (1 L) and RT heptane (1 L), and dry to yield 683.5 g (96.7%) of the title compound as light purple solid. 1H-NMR(DMSO-d6, 300 MHz), δ 10.79 (br s, 1H), 9.42 (br s, 1H), 7.20-7.56 (m, 8H), 6.92 (t, 1H), 6.41 (dd, 1H), 5.18(s, 1H).

Workup

  1. customEquip
  2. additionapparatus, addition funnel
  3. customThoroughly purge the flask with nitrogen
  4. temperatureAfter cooling the biphasic solution to less than 10° C.
  5. temperatureto maintain the temperature at less than 10° C. over one hour
  6. stirringStir
  7. customthe reaction vigorously for 1 hour until complete by TLC
  8. customSeparate the layers
  9. extractionextract the aqueous layer with CH2Cl2 (1.7 L)
  10. washCombine the organic layers, wash with 2N NaOH (2×2 L)
  11. dry with materialdry over Na2SO4
  12. filtrationAfter filtering off the drying agent
  13. concentrationconcentrate the filtrate in vacuo to a volume of ˜1.5 L
  14. customresulting in thin dark mixture
  15. customto form a thick sand-like slurry
  16. concentrationConcentrate to a volume of ˜1.5 L
  17. filtrationfilter while hot (50-60° C.)
  18. washwash
  19. temperaturewith warm (45° C.) heptane (1 L) and RT heptane (1 L)
  20. customdry

Sources & evidence

ORD record
ord-7ff8ead1ec8b4384bcf3a1137f781b2c
Source dataset
uspto-grants-2010_06
Patent number
US07728150B2

Linked notes

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