Ethanol → HCID 9814205, compound

HRID 991276Notes

Reaction equation

HRID 991276 reaction equation
[CH2:1]([O:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][C@H:9]([NH:14][C:15](=O)[C:16](F)(F)F)[C:10]2=[O:13])=[CH:6][CH:5]=1)[CH3:2].[BH4-].[Na+].[O-]P([O-])([O-])=O.[Na+].[Na+].[Na+].[CH2:31](Br)[CH2:32][CH3:33].[CH2:35](O)C>>[CH2:15]([N:14]([CH2:31][CH2:32][CH3:33])[C@H:9]1[CH2:8][C:7]2[C:11](=[CH:12][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=2)[C@@H:10]1[OH:13])[CH2:16][CH3:35]

Participants

6

Reactant 5

HCID 702EthanolHCID 78401-BromopropaneHCID 24243Trisodium PhosphateHCID 4311764Sodium borohydrideHCID 9900550HCID 9900550, compound

Product 1

HCID 9814205HCID 9814205, compound

Procedure

N-[(2S)-6-Ethoxy-2,3-dihydro-1-oxo-1H-inden-2-yl]-2,2,2-trifluoroacetamide (V, EXAMPLE 4, 4.13 g, 15 mmol) is suspended in ethanol (45 ml) and cooled to −15°. Sodium borohydride (2.83 g, 75 mmol, 5 equiv.) is added and the reaction mixture gradually warmed to 20-25° overnight. The reaction mixture is concentrated to dryness and then suspended in acetonitrile (105 ml). Sodium phosphate tribasic (8.12 g, 49.5 mmol, 3.3 equivalents) is added and the mixture heated to 40°. n-Propylbromide (12.26 ml, 135 mmol, 9 equivalents) is added and reaction is heated to 65°. Heating is continued for 48 hr. The reaction mixture is filtered and the filtrate concentrated. The concentrate is partitioned in methyl t-butyl ether (100 ml) and sodium hydroxide (1 M, 50 ml). The organic layer is collected and acidified with hydrochloric acid (3 M, 50 ml). The aqueous phase is collected and the pH is adjusted to 13 using sodium hydroxide (50%, 25 ml). The product is extracted into methyl t-butyl ether (100 ml) and concentrated to give the title compound. TLC Rf=0.9 (ammonium hydroxide/methanolnmethylene chloride. 1.5/13.5/85); NMR δ7.04, 6.90, 6.79, 5.04, 4.01, 3.39, 2.87, 2.72, 2.59-2.48, 1.54-1.48, 1.39 and 0.90; CMR δ158.4, 144.2, 131.5, 125.6, 115.4, 109.2, 77.3, 73.2, 63.6, 53.6, 29.9, 21.1, 14.8, 11.9; MS (CI, NH3) m/z (relative intensity) 278 (100), 248 (70), 236 (20).

Workup

  1. temperaturecooled to −15°
  2. temperaturethe reaction mixture gradually warmed to 20-25° overnight
  3. concentrationThe reaction mixture is concentrated to dryness
  4. temperaturethe mixture heated to 40°
  5. customreaction
  6. temperatureis heated to 65°
  7. temperatureHeating
  8. filtrationThe reaction mixture is filtered
  9. concentrationthe filtrate concentrated
  10. customThe concentrate is partitioned in methyl t-butyl ether (100 ml)
  11. customThe organic layer is collected
  12. customThe aqueous phase is collected
  13. extractionThe product is extracted into methyl t-butyl ether (100 ml)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-1ddd357798a34d82887b0003cd1bf35b
Source dataset
uspto-grants-2002_10
Patent number
US06462234B2

Reaction notes

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