Diisopropylethylamine → 5-(3-Hydroxypyrrolidin-1-yl)-2-nitropyridine

HRID 2236192Notes

Reaction equation

HRID 2236192 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][N:5]=1)([O-:3])=[O:2].C(N(C(C)C)CC)(C)C.[OH:20][C@H:21]1[CH2:25][CH2:24][N:23](O)[CH2:22]1>CCO>[N+:1]([C:4]1[N:5]=[CH:6][C:7]([N:23]2[CH2:24][CH2:25][CH:21]([OH:20])[CH2:22]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 8176205-Bromo-2-nitropyridineHCID 54124651(S)-3-hydroxypyrrolidinol

Product 1

HCID 629183315-(3-Hydroxypyrrolidin-1-yl)-2-nitropyridineYield 47.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 2-nitro-5-bromopyridine (320 mg, 2.02 mmol) in EtOH (6 mL) was treated with diisopropylethylamine (710 μL, 520 mg, 4.04 mmol) and (S)-3-hydroxypyrrolidinol (350 mg, 4.04 mmol). The mixture was heated in a sealed tube at 85° C. for 21.5 h then cooled and partitioned between CH2Cl2 and water. The organic layer was dried over Na2SO4, filtered and concentrated and the residue was chromatographed on a silica gel column with a 40-100% EtOAc in hexanes to 0-30% THF in EtOAc gradient to afford the product, as a yellow solid (200 mg, 47% yield). HRMS m/z calcd for C9H11N3O3 [M+H]+: 210.0873; Found: 210.0873.

Workup

  1. temperaturethen cooled
  2. custompartitioned between CH2Cl2 and water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was chromatographed on a silica gel column with a 40-100% EtOAc in hexanes to 0-30% THF in EtOAc gradient
  7. customto afford the product

Sources & evidence

ORD record
ord-11e1a80a67c4479b867fa0f89c8c2e05
Source dataset
uspto-grants-2010_05
Patent number
US07714126B2

Reaction notes

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