4-Fluoroaniline → (4R,4aR,8aR)-4-[(4-fluorophenyl)amino]octahydro-4-aH-isochromen-4a-ol

HRID 73627Notes

Reaction equation

HRID 73627 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.C[Al](C)C.[O:13]1[C:23]23[C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22]2)[CH2:17][O:16][CH2:15][C@H:14]13>C(Cl)Cl>[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C@H:14]2[C@:23]3([OH:13])[C@H:18]([CH2:19][CH2:20][CH2:21][CH2:22]3)[CH2:17][O:16][CH2:15]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 16682925TrimethylaluminumHCID 86668657HCID 86668657, compound

Product 1

HCID 52911327(4R,4aR,8aR)-4-[(4-fluorophenyl)amino]octahydro-4-aH-isochromen-4a-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-fluoroaniline (0.721 g, 6.48 mmol) in CH2Cl2 (6 mL) at 0° C. was added trimethylaluminum (2M in toluene, 3.24 mL) dropwise. The mixture was warmed to rt for 30 min. A mixture of both cis and trans octahydrooxireno[d]isochromene (0.200 g, 1.30 mmol) in CH2Cl2 2 mL+0.5 mL rinse) was then added and the mixture was stirred at rt overnight. The reaction was cooled to 0° C. and treated with 50% NaOH (1 mL) then water (1 mL). The mixture was diluted with more water and extracted 3× with CH2Cl2. The combined organics were dried (anhd. Na2SO4), filtered, and concentrated. The residue was purified by column chromatography to give the title compound. 1H NMR (500 MHz, CDCl3) δ 6.94 (1, 2H, J=8.6 Hz), 6.78 (dd, 2H, J=4.2 Hz, 8.8 Hz), 4.14 (dd, 1H, J=1.5 Hz, 12.0 Hz), 3.64 (d, 1H, J=11.5 Hz), 3.56 (dd, 1H, J=4.6 Hz, 11.0), 3.48 (t, 1H, J=11.5 Hz), 3.10 (s, 1H), 1.17-2.00 (m, 9H). HRMS (ES) m/z M+H calc'd.: 266.1551. found: 266.1554

Workup

  1. washrinse)
  2. additionwas then added
  3. temperatureThe reaction was cooled to 0° C.
  4. additiontreated with 50% NaOH (1 mL)
  5. additionThe mixture was diluted with more water
  6. extractionextracted 3× with CH2Cl2
  7. dry with materialThe combined organics were dried (anhd. Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2c1f9f1629524a2fae648bea43e04d09
Source dataset
uspto-grants-2014_09
Patent number
US08829196B2

Reaction notes

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