Hydrazine hydrate (1:1) → ((2S,4R)-2-(aminomethyl)-4-hydroxypyrrolidin-1-yl)(biphenyl-2-yl)methanone

HRID 60786Notes

Reaction equation

HRID 60786 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:2]([C:7]([N:9]2[CH2:13][C@H:12]([OH:14])[CH2:11][C@H:10]2[CH2:15][N:16]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.O.NN>CO>[NH2:16][CH2:15][C@@H:10]1[CH2:11][C@@H:12]([OH:14])[CH2:13][N:9]1[C:7]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:8]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 897481992-(((2S,4R)-1-(biphenylcarbonyl)-4-hydroxypyrrolidin-2-yl)methyl)isoindoline-1,3-dione

Product 1

HCID 89748273((2S,4R)-2-(aminomethyl)-4-hydroxypyrrolidin-1-yl)(biphenyl-2-yl)methanoneYield 66%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of the above mentioned 2-(((2S,4R)-1-(biphenylcarbonyl)-4-hydroxypyrrolidin-2-yl)methyl)isoindoline-1,3-dione (˜5.6 mmol) and hydrazine monohydrate (0.65 mL, 10 mmol) in MeOH was stirred at 70° C. for 4 h. The resulting white suspension was cooled to rt, filtered and the filtrate was concentrated in vacuo to a white solid, which was purified by column chromatography on silica gel (100% MeOH) to provide ((2S,4R)-2-(aminomethyl)-4-hydroxypyrrolidin-1-yl)(biphenyl-2-yl)methanone as a white solid (1.1 g, 66% yield over two steps. MS (ESI) 297.05 (M+H).

Workup

  1. additionA mixture of the
  2. temperatureThe resulting white suspension was cooled to rt
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated in vacuo to a white solid, which
  5. customwas purified by column chromatography on silica gel (100% MeOH)

Sources & evidence

ORD record
ord-0d6368f843c2499dbf5bd01c6e7296eb
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

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