1,2-Dichloroethane → diethyl 2-(5-bromo-8-carbamoyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)malonate

HRID 523281Notes

Reaction equation

HRID 523281 reaction equation
[Br:1][C:2]1[C:14]([F:15])=[CH:13][C:12]([C:16](O)=[O:17])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([CH:19]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:8][C:9]=1[NH:10]2.C(Cl)CCl.C1C=CC2N(O)N=[N:40]C=2C=1.[NH4+].[OH-]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[C:14]([F:15])=[CH:13][C:12]([C:16](=[O:17])[NH2:40])=[C:11]2[C:3]=1[C:4]1[CH2:5][CH2:6][CH:7]([CH:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:8][C:9]=1[NH:10]2

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 14923Ammonium HydroxideHCID 757711-HydroxybenzotriazoleHCID 1177610905-bromo-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid

Product 1

HCID 117761074diethyl 2-(5-bromo-8-carbamoyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)malonate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-2-(1,3-diethoxy-1,3-dioxopropan-2-yl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-8-carboxylic acid (0.981 g, 2.09 mmol), EDC (0.600 g, 3.13 mmol) and HOBT (0.383 g, 2.50 mmol) in THF (5 mL) was stirred at room temperature for 60 min. The mixture was treated with NH4OH (1.74 mL, 12.5 mmol) and stirred at room temperature overnight. The mixture was diluted with EtOAc, washed sequentially with saturated aqueous Na2CO3 and brine. The combined aqueous layers were extracted with EtOAc, and the combined organic phases were dried and concentrated. The residue was purified by column chromatography on silica gel (40 g), eluting with EtOAc-hexanes (gradient from 0-100%), to provide diethyl 2-(5-bromo-8-carbamoyl-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-2-yl)malonate as a slightly yellow solid (440 mg, 45% yield). Mass spectrum m/z 469, 471 (M+H)+.

Workup

  1. stirringstirred at room temperature overnight
  2. washwashed sequentially with saturated aqueous Na2CO3 and brine
  3. extractionThe combined aqueous layers were extracted with EtOAc
  4. customthe combined organic phases were dried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (40 g)
  7. washeluting with EtOAc-hexanes (gradient from 0-100%)

Sources & evidence

ORD record
ord-e931161b1f2f487ab036bae4f31cf608
Source dataset
uspto-grants-2016_05
Patent number
US09334290B2

Reaction notes

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