1,2-Dichloroethane → (R)-3-[N-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1402294Notes

Reaction equation

HRID 1402294 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[CH3:10][C:11]([O:14][C:15]([N:17]1[CH2:21][C@H:20]([C:22](O)=[O:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])[CH3:12].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.O>[C:11]([O:14][C:15]([N:17]1[CH2:18][CH2:19][C@@H:20]([C:22]([N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)[NH2:9])=[O:23])[CH2:21]1)=[O:16])([CH3:13])([CH3:12])[CH3:10]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 1512491(3R)-1-[(tert-butoxy)carbonyl]pyrrolidine-3-carboxylic acidHCID 199167865-Fluoro-2-hydrazinylpyridine

Product 1

HCID 86687138(R)-3-[N-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a brown solution of (5-fluoro-pyridin-2-yl)-hydrazine (590 mg, 4.64 mmol), (R)-1-N-BOC-beta proline (Manchester Organics, 1.00 g, 4.64 mmol) and HOBt.H2O (71.1 mg, 0.464 mmol) in DCM (20 mL) at RT was added EDC (1.07 g, 5.57 mmol) (CARE: exotherm to 35° C.) and the resulting solution stirred at RT for 4 h. Water (20 mL) was added and the mixture shaken. The aqueous was extracted with DCM (20 mL), then the combined organics were passed through a hydrophobic frit and concentrated in vacuo to 1 mL volume. FCC, using 1-10% MeOH in DCM, gave the title compound as a pale brown foam (1.37 g, 91%). LCMS (Method 3): Rt 2.93 min, m/z 347 [MNa+].

Workup

  1. stirringthe mixture shaken
  2. extractionThe aqueous was extracted with DCM (20 mL)
  3. concentrationconcentrated in vacuo to 1 mL volume

Sources & evidence

ORD record
ord-37d8e1010b694683875fdf9e1909d153
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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