1,2-Dichloroethane → (S)-1-Ethyl-pyrrolidine-2-carboxylic acid N-(5-fluoro-pyridin-2-yl)-hydrazide

HRID 1402209Notes

Reaction equation

HRID 1402209 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH2:10]([N:12]1[CH2:16][CH2:15][CH2:14][C@H:13]1[C:17](O)=[O:18])[CH3:11].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([C:17]([C@@H:13]2[CH2:14][CH2:15][CH2:16][N:12]2[CH2:10][CH3:11])=[O:18])[NH2:9])=[N:6][CH:7]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 199167865-Fluoro-2-hydrazinylpyridineHCID 283547181-ethyl-L-Proline

Product 1

HCID 117722834(S)-1-Ethyl-pyrrolidine-2-carboxylic acid N-(5-fluoro-pyridin-2-yl)-hydrazideYield 54.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (178 mg, 1.39 mmol) in DMF (10.0 mL) was added (S)-1-ethyl-pyrrolidine-2-carboxylic acid (200 mg, 1.39 mmol), EDC (293 mg, 1.53 mmol) and HOBt.H2O (18.0 mg, 0.14 mmol). The reaction was stirred for 4 h then partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (190 mg, 54%). LCMS (Method 4): Rt 0.29 min, m/z 253.1 [MH+].

Workup

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was then extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-6350601b7bbf4002904adf909ae356ac
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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