N-Formylmorpholine → 6-Bromo-9-(2-(2-methoxyethoxy)ethyl)-9H-carbazole-3-carbaldehyde

HRID 1774087Notes

Reaction equation

HRID 1774087 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][C:10](F)=[CH:9][CH:8]=3.[Li]CCCC.[CH:28](N1CCOCC1)=[O:29]>C1COCC1>[Br:1][C:2]1[CH:14]=[C:13]2[C:5](=[CH:4][CH:3]=1)[N:6]([CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[C:7]1[CH:8]=[CH:9][C:10]([CH:28]=[O:29])=[CH:11][C:12]2=1

Participants

5

Reactant 3

HCID 20417N-FormylmorpholineHCID 867279573-Bromo-6-fluoro-9-(2-(2-methoxyethoxy)ethyl)-9H-carbazoleHCID 178418339Butyllithium

Product 1

HCID 867279596-Bromo-9-(2-(2-methoxyethoxy)ethyl)-9H-carbazole-3-carbaldehydeYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromo-6-fluoro-9-(2-(2-methoxyethoxy)ethyl)-9H-carbazole (3.4 g, 9.3 mmol) in dry THF (50 ml) was added n-BuLi (1.6 M, 8.7 ml, 13.9 mmol) at −78° C. The resulting mixture was stirred for 50 min at −78° C. and then added with N-formylmorpholine (1.86 ml, 18.6 mmol). The reaction mixture was allowed to warm to rt and stirred for 2 h before quenched with ammonia chloride solution. The organic layer was separated, dried over anhydrous sodium sulfate and evaporated under vacuum. The residue was purified by silica gel column chromatography eluting with 2:1 petroleum ether/ethyl acetate to give compound 7 in 65% yield. 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.53 (s, 1H), 8.02-8.00 (m, 1H), 7.80-7.77 (m, 1H), 7.54 (d, J=8.8 Hz, 1H), 7.45 (dd, J=4.0 Hz, J=9.2 Hz 1H), 7.28-7.23 (m, 1H), 4.52 (t, J=5.6 Hz, 2H), 3.88 (t, J=5.6 Hz, 2H), 3.52-3.50 (m, 2H), 3.40 (d, J=2.8 Hz, 2H), 3.28 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 191.8, 159.3, 156.9, 145.2, 137.8, 128.8, 127.5, 124.4, 123.7, 123.7, 123.7, 122.8, 114.8, 114.5, 110.6, 110.5, 109.8, 106.7, 106.4, 72.1, 71.0, 69.5, 59.2, 43.9. HRMS (MALDI-TOF) m/z Calcd for C18H18FNO3 316.1343 Found 316.1340[M]+.

Workup

  1. temperatureto warm to rt
  2. stirringstirred for 2 h
  3. custombefore quenched with ammonia chloride solution
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated under vacuum
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with 2:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-aa0a5259aa8c42e5bfff5d4ecf5e5464
Source dataset
uspto-grants-2016_02
Patent number
US09255933B2

Reaction notes

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