N-(2-fluoroethyl)aniline → 9-(2-Fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester

HRID 1506697Notes

Reaction equation

HRID 1506697 reaction equation
[F:1][CH2:2][CH2:3][NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:11]([O:13][C:14]([C:16]1[CH2:21][CH2:20][CH2:19][CH:18](Br)[C:17]=1O)=[O:15])[CH3:12]>CC(O)C.[Cl-].[Zn+2].[Cl-]>[CH2:11]([O:13][C:14]([CH:16]1[C:17]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]([CH2:3][CH2:2][F:1])[C:18]=2[CH2:19][CH2:20][CH2:21]1)=[O:15])[CH3:12]

Participants

5

Reactant 2

HCID 14524N-(2-fluoroethyl)anilineHCID 590519613-Bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester

Product 1

HCID 666792469-(2-Fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (2-fluoro-ethyl)-phenyl-amine (24; prepared according to Example 4(a)) (560 mg, 4.0 mmol) and 3-bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester (29) (500 mg, 2.0 mmol) was stirred under N2 at 50° C. for 3 h and the reaction turned brown. The resulting mixture was dissolved in propan-2-ol (4 mL) and dry zinc chloride (820 mg, 6 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The product was dissolved in ethyl acetate/ether (30 mL/150 mL) and washed with 2 N HCl (40 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL) then dried and concentrated to afford 447 mg (91%) of 9-(2-fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester (30) as a yellow oil which was used in the next step without purification. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 14.3, 20.4, 21.7, 26.4, 38.5, 43.1 (d, TCF=15 Hz), 60.6, 76.6, 77.0, 77.4, 82.1 (d, JCF=173 Hz), 106.9, 108.5, 118.9, 119.4, 121.1, 127.1, 136.2, 136.7, 174.9.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux under N2 for 16 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe product was dissolved in ethyl acetate/ether (30 mL/150 mL)
  5. washwashed with 2 N HCl (40 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL)
  6. customthen dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-79cc32ed2c3d491aaa419a32bd0b9109
Source dataset
uspto-grants-2015_12
Patent number
US09220795B2

Reaction notes

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