HCID 58194817, compound → HCID 66679731, compound

HRID 1753944Notes

Reaction equation

HRID 1753944 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([N:22]([CH2:33][CH3:34])[C:23]([CH:25]1[CH2:30][CH2:29][CH2:28][CH:27](Br)[C:26]1=O)=[O:24])[CH3:21]>CC(O)C.[Cl-].[Zn+2].[Cl-]>[CH2:33]([N:22]([CH2:20][CH3:21])[C:23]([CH:25]1[C:26]2[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=3)[N:12]([CH2:10][CH2:9][O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:27]=2[CH2:28][CH2:29][CH2:30]1)=[O:24])[CH3:34]

Participants

5

Reactant 2

HCID 58194817HCID 58194817, compoundHCID 66679440HCID 66679440, compound

Product 1

HCID 66679731HCID 66679731, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-benzyloxy-N-(4-fluoro-phenyl)-acetamide (33) (5.3 g, 22 mmol) and 3-bromo-2-oxo-cyclohexanecarboxylic acid diethylamide (35) (3.0 g, 13 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 (30 mL) and dry zinc chloride (9.0 g, 66 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (300 mL) and washed with 2 N HCl (100 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL) then dried and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (10-50% B, 100 g) to afford 196 mg (11%) of 9-(2-benzyloxy-ethyl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid diethylamide (36) as a white solid. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δH 1.14 (3H, t, J=7 Hz, N(CH2CH3)2), 1.30 (3H, t, J=7 Hz, N(CH2CH3)2), 1.60-2.60 (4H, m, 2- and 3-CH2), 2.70-2.85 (2H, m, 1-CH2), 3.10-3.65 (4H, m, N(CH2CH3)2 and NCH2CH2OBn), 3.66-3.75 (1H, m, 4-CH), 4.00-4.25 (2H, m, NCH2CH2OBn), 4.41 (2H, s, OCH2Ph), 6.75-6.95 (2H, m, NCCHCHCFCH), 7.05-7.15 (1H, m, NCCHCHCFCH), and 7.16-7.25 (5H, m, Ph).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux under N2 for 16 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (300 mL)
  5. washwashed with 2 N HCl (100 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL)
  6. customthen dried
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with petrol (A) and ethyl acetate (B) (10-50% B, 100 g)

Sources & evidence

ORD record
ord-9a8a19b26e4d49dfaa86e9af6828701b
Source dataset
uspto-grants-2015_10
Patent number
US09168317B2

Reaction notes

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