Sodium Hydroxide → 9-(2-fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid

HRID 1753939Notes

Reaction equation

HRID 1753939 reaction equation
C([O:3][C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:19][CH2:20][F:21])[C:10]=2[CH2:9][CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+]>C(O)C.O>[F:21][CH2:20][CH2:19][N:11]1[C:10]2[CH2:9][CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[C:18]=2[C:17]2[C:12]1=[CH:13][CH:14]=[CH:15][CH:16]=2

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 666792469-(2-Fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester

Product 1

HCID 666800789-(2-fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acidYield 38.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

9-(2-Fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester (30) (380 mg, 1.3 mmol) was dissolved in ethanol (3 mL) and then NaOH (520 mg) in water (5 mL) was added. The reaction was heated at reflux for 2 h. The reaction was concentrated in vacuo and the residue diluted with water and washed with dichloromethane (2×50 mL). The aqueous layer was added drop wise to 2 N HCl (50 mL) and then extracted into dichloromethane (3×50 mL). The organics were dried and concentrated in vacuo to afford 130 mg (37%) of 9-(2-fluoro-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid (31) as a yellow solid which was used in the next step without purification. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δ 1.90-2.42 (4H, m, 2- and 3-CH2), 2.60-2.91 (2H, m, 1-CH2), 3.94 (1H, t, J=6 Hz, 4-CH), 4.30 (1H, t, J=6 Hz, NCH2CH2F), 4.37 (1H, t, J=6 Hz, NCH2CH2F), 4.59 (1H, t, J=6 Hz, NCH2CH2F), 4.74 (1H, t, J=6 Hz, NCH2CH2F), 7.05-7.26 (3H, m, ArH), 7.59 (1H, d, J=9 Hz, ArH).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 2 h
  3. concentrationThe reaction was concentrated in vacuo
  4. additionthe residue diluted with water
  5. washwashed with dichloromethane (2×50 mL)
  6. additionThe aqueous layer was added drop wise to 2 N HCl (50 mL)
  7. extractionextracted into dichloromethane (3×50 mL)
  8. customThe organics were dried
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bf428697b5674369b0f303876f8f75ac
Source dataset
uspto-grants-2015_10
Patent number
US09168317B2

Reaction notes

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