Ammonia → (2R,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1S)-1-aminoethyl) pyrrolidine

HRID 501617Notes

Reaction equation

HRID 501617 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C:21](=[N:23]O)[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].N>CO.O.[Ni].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([NH2:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 222AmmoniaHCID 86594305HCID 86594305, compound

Product 1

HCID 16732284(2R,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1S)-1-aminoethyl) pyrrolidineYield 63.8%

Reagents, catalysts & solvents 4

HCID 935NickelCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 962WaterSolvent2×

Procedure

To a solution of 61E (3.6 g, 10.0 mmol) in methanol in a pressure vessel was added Raney Ni in water (˜0.2 g), 10% Pd/C (Degussa type, 200 mg), water (7.5 mL) and ammonia in methanol (2.0M, 5 mL). The reaction vessel was carefully evacuated under vacuum until the solvent bubbled gently. Hydrogen gas was then introduced to a pressure of 70 psi and the reaction was stirred for 2 min). The reaction vessel was again carefully evacuated under vacuum until the solvent bubbled gently. Hydrogen gas was then introduced to a pressure of 70 psi and the reaction was stirred for 18 h at rt. The reaction was filtered through a pad of celite, taking care to keep the captured catalyst wet with methanol at all times. The celite pad was washed with methanol until the product could no longer be detected in the eluent (TLC, 5% MeOH in CH2Cl2, stain with ninhydrin and heat). Solvent was removed under vacuum and purification by flash chromatography (110 g ISCO silica gel cartridge, step gradient 0%-5%-10% MeOH in CH2Cl2) gave the title compound (2.2 g): MS (ES) m/z 345.35 [M+H]+

Workup

  1. customThe reaction vessel was carefully evacuated under vacuum until the solvent
  2. custombubbled gently
  3. additionHydrogen gas was then introduced to a pressure of 70 psi
  4. customThe reaction vessel was again carefully evacuated under vacuum until the solvent
  5. custombubbled gently
  6. additionHydrogen gas was then introduced to a pressure of 70 psi
  7. stirringthe reaction was stirred for 18 h at rt
  8. filtrationThe reaction was filtered through a pad of celite
  9. washThe celite pad was washed with methanol until the product
  10. temperaturecould no longer be detected in the eluent (TLC, 5% MeOH in CH2Cl2, stain with ninhydrin and heat)
  11. customSolvent was removed under vacuum and purification by flash chromatography (110 g ISCO silica gel cartridge, step gradient 0%-5%-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-c09a91915b0c4d2385f1f5d66e64a8b2
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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