Hydrochloric Acid → N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamide

HRID 2242330Notes

Reaction equation

HRID 2242330 reaction equation
[C:1]([NH:4][C@@H:5]1[CH2:10][C@H:9]([N:11]([CH:13]([CH3:15])[CH3:14])[CH3:12])[CH2:8][CH2:7][C@@H:6]1[N:16]1[CH2:20][CH2:19][C@H:18]([NH:21]C(=O)OCC2C=CC=CC=2)[C:17]1=[O:32])(=[O:3])[CH3:2].Cl>CC(O)C.[Pd]>[NH2:21][C@H:18]1[CH2:19][CH2:20][N:16]([C@H:6]2[CH2:7][CH2:8][C@@H:9]([N:11]([CH:13]([CH3:15])[CH3:14])[CH3:12])[CH2:10][C@H:5]2[NH:4][C:1](=[O:3])[CH3:2])[C:17]1=[O:32]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 44185160benzyl (S)-1-((1S,2R,4R)-2-acetamido-4-(isopropyl(methyl)amino)cyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Product 1

HCID 44185161N-((1R,2S,5R)-2-((S)-3-amino-2-oxopyrrolidin-1-yl)-5-(isopropyl(methyl)amino)cyclohexyl)acetamideYield 130.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent

Procedure

Example 1, Alternative Preparation, Step 6: To a solution containing acetamide 10 (˜61 g) in i-PrOH (˜625 mL) was added 10% Pd/C wet catalyst (2.5 g) and the suspension was hydrogenated at 30 psig and approx. 25° C. for at least 2 h. Upon completion (HPLC), the catalyst was removed by filtration and the filtrate was concentrated to approx. 550 mL. Water (8.8 mL) was added, followed by 5.6 N hydrochloric acid in i-PrOH solution (69.5 mL). The resulting slurry was held at room temperature overnight. The product was isolated by filtration and the cake was rinsed with i-PrOH (2×100 mL) and dried in vacuo to constant weight at ˜50° C. to give N-[(1R,2S,5R)-2-((S)-3-amino-2-oxo-pyrrolidin-1-yl)-5-(isopropyl-methyl-amino)-cyclohexyl]-acetamide 11 (55.6 g, 97% yield) as its hydrochloric acid salt (73.6% free base assay, HPLC).

Workup

  1. customExample 1, Alternative Preparation, Step 6
  2. waitthe suspension was hydrogenated at 30 psig and approx. 25° C. for at least 2 h
  3. customUpon completion (HPLC), the catalyst was removed by filtration
  4. concentrationthe filtrate was concentrated to approx. 550 mL
  5. additionWater (8.8 mL) was added
  6. customThe product was isolated by filtration
  7. washthe cake was rinsed with i-PrOH (2×100 mL)
  8. customdried in vacuo to constant weight at ˜50° C.

Sources & evidence

ORD record
ord-84e12e625b17401ab6c696b7f3ba13ed
Source dataset
uspto-grants-2010_03
Patent number
US07671062B2

Reaction notes

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