Water → HCID 67772316, compound

HRID 1808786Notes

Reaction equation

HRID 1808786 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[NH2:7][C@@H:8]([CH:18]([CH3:20])[CH3:19])[C:9]([N:11]1[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12]1)=O.O.[OH-].[Na+]>C1COCC1>[F:17][C:13]1([F:16])[CH2:14][CH2:15][N:11]([CH2:9][C@@H:8]([NH2:7])[CH:18]([CH3:19])[CH3:20])[CH2:12]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 67772991HCID 67772991, compound

Product 1

HCID 67772316HCID 67772316, compoundYield 70.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a 1M solution of LAH in THF (9.89 mL, 9.89 mmol) was (S)-2-amino-1-(3,3-difluoropyrrolidin-1-yl)-3-methylbutan-1-one (1.02 g, 4.95 mmol) dropwise added (over approximately 60 min) as a solution in THF under a nitrogen atmosphere. The mixture was stirred at rt for 30 min and heated at 70° C. over night. The reaction was cooled to 0° C. Water (0.5 mL) was slowly added, followed by 15% aq. NaOH (0.5 mL), THF (10 mL) and additional water (2 mL). The reaction mixture was warmed to rt and stirred for 1 h. The mixture was filtered and the solid washed with THF. The filtrate was dried (Na2SO4) and concentrated under reduced pressure to give the title compound (0.67 g, 70.6%). The obtained crude product was used without further purification. 1H NMR (400 MHz, CH3OD) δ 0.87-0.99, 1.52-1.65, 2.12-2.48, 2.59-2.87, 2.92-3.07, 3.31-3.67.

Workup

  1. temperatureheated at 70° C. over night
  2. temperatureThe reaction was cooled to 0° C
  3. temperatureThe reaction mixture was warmed to rt
  4. stirringstirred for 1 h
  5. filtrationThe mixture was filtered
  6. washthe solid washed with THF
  7. dry with materialThe filtrate was dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5321fc6973c14debb2bae6ea5141c035
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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