HCID 1123811, compound → HCID 59004674, compound

HRID 1668487Notes

Reaction equation

HRID 1668487 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O[C:15]([N:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[C:22](=O)[NH:23][C:24]1[CH:29]=[CH:28][C:27]([Br:30])=[CH:26][CH:25]=1)=O)C1C=CC=CC=1>O1CCCC1>[Br:30][C:27]1[CH:28]=[CH:29][C:24]([NH:23][CH2:22][C@@H:18]2[CH2:19][CH2:20][CH2:21][N:17]2[CH3:15])=[CH:25][CH:26]=1

Participants

4

Reactant 2

HCID 1123811HCID 1123811, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 59004674HCID 59004674, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium aluminum hydride (0.263 g, 6.943 mmol) and anhydrous tetrahydrofuran (10 mL) were charged to a dry argon purged flask fitted with magnetic stir bar, condenser and dropping funnel and the mixture cooled to 0° C. A solution of compound 99 (0.70 g, 1.736 mmol) in anhydrous tetrahydrofuran (15 mL) is charged to the dropping funnel and added dropwise to the cold solution over 20 minutes. The resulting mixture was allowed to warm to room temperature over 90 minutes then heated to reflux for 45 minutes. After cooling to room temperature, then to 0° C., the reaction was quenched by the portionwise addition of sodium sulfate decahydrate (approximately 4.0 g). Water (5 mL) and ethylacetate (50 mL) were added and mixture stirred overnight, transferred to a separatory funnel (washing with a small amount of water and ethyl acetate) and the organic layer separated. The aqueous layer was further extracted with ethyl acetate and the combined organic layers washed with brine, dried over sodium sulfate, concentrated and the residue purified via chromatography on silica gel (MeOH:CH2Cl2, 3:97 to 1:9) to yield compound 100 (308 mg, 66.0%) as a pale yellow oil. 1H NMR (DMSO-d6) δ 1.48-1.67 (2×m, 3H), 1.83-1.95 (m, 1H), 2.14 (q, 1H, J=8.6 Hz), 2.28 (s, 3H), 2.32-2.38 (m, 1H), 2.81-2.89 (m, 1H), 2.93-2.99 (m, 1H), 3.10-3.17 (m, 1H), 5.54-5.66 (m, 1H), 6.55 (d, 2H, J=8.9 Hz), 7.17 (d, 2H, J=8.9 Hz); ESI-MS (m/z, %): 269/271 (MH+, 100%).

Workup

  1. customfitted with magnetic stir bar, condenser
  2. additionadded dropwise to the cold solution over 20 minutes
  3. temperatureto warm to room temperature over 90 minutes
  4. temperaturethen heated
  5. temperatureto reflux for 45 minutes
  6. temperatureAfter cooling to room temperature
  7. customto 0° C., the reaction was quenched by the portionwise addition of sodium sulfate decahydrate (approximately 4.0 g)
  8. additionWater (5 mL) and ethylacetate (50 mL) were added
  9. customtransferred to a separatory funnel
  10. wash(washing with a small amount of water and ethyl acetate) and the organic layer
  11. customseparated
  12. extractionThe aqueous layer was further extracted with ethyl acetate
  13. washthe combined organic layers washed with brine
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customthe residue purified via chromatography on silica gel (MeOH:CH2Cl2, 3:97 to 1:9)

Sources & evidence

ORD record
ord-add8ec7c0aa64e01b5964ecca095692d
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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