1,2-Dichloroethane → ethyl 6-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate

HRID 2410667Notes

Reaction equation

HRID 2410667 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](O)=[O:16])[CH:14]=1)[NH:11][C:10]1[CH2:9][CH:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:7][CH2:6][C:5]2=1.C(Cl)CCl.O.O[N:29]1C2C=CC=CC=2N=N1.[OH-].[NH4+]>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:16])[NH2:29])[CH:14]=1)[NH:11][C:10]1[CH2:9][CH:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:7][CH2:6][C:5]2=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 27960291-Hydroxybenzotriazole hydrateHCID 666048536-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid

Product 1

HCID 66605605ethyl 6-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylateYield 97.5%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

To a suspension of 6-bromo-2-(ethoxycarbonyl)-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (18.5 g, 42.4 mmol), EDC (10.58 g, 55 2 mmol), and 1-hydroxybenzotriazole hydrate (8.45 g, 55.2 mmol) in THF/CH2Cl2 (5/1) (480 mL) was added ammonium hydroxide (9.91 mL, 76 mmol) and it turned into a thick light yellow suspension and it was stirred at room temperature over the weekend. CAUTION: A mild exotherm was observed. The reaction mixture warmed up to 31° C. If reaction is done on larger scale, consider cooling or slow addition of one of the reagents. The reaction mixture was concentrated and then titurated with 500 ml water (sonicate for 2 minutes), then filtered through a medium porosity glass frit. The solids were washed with water and dried in a nitrogen stream to give 15.1 g ethyl 6-bromo-8-carbamoyl-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylate. MS (ESI) m/e−=363/365, m/e+=365/367 [1Br isotope pattern]. 1H NMR (DMSO-d6) δ ppm 10.97 (s, 1H), 8.10 (b, 1H), 7.74 (d, 1H, J=1.8), 7.68 (d, 1H, J=1.5), 7.44 (b, 1H), 4.16-4.06 (m, 2H), 3.04 (dd, 1H, J=16.2, 5.0), 2.95-2.83 (m, 2H), 2.75-2.68 (m, 1H), 2.67-2.58 (m, 1H), 2.18-2.12 (m, 1H), 1.87-1.79 (m, 1H), 1.21 (t, 3H, J=7.0).

Workup

  1. temperatureThe reaction mixture warmed up to 31° C
  2. customIf reaction
  3. temperatureconsider cooling
  4. additionslow addition of one of the reagents
  5. concentrationThe reaction mixture was concentrated
  6. customtiturated with 500 ml water (sonicate for 2 minutes)
  7. filtrationfiltered through a medium porosity glass frit
  8. washThe solids were washed with water
  9. customdried in a nitrogen stream

Sources & evidence

ORD record
ord-8f8a59fe3a304d98b8171c4c537380f4
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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