1,2-Dichloroethane → (R)-3-[N'-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-morpholine-4-carboxylic acid tert-butyl ester

HRID 2285090Notes

Reaction equation

HRID 2285090 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]1[C:23](O)=[O:24])=[O:16])([CH3:13])([CH3:12])[CH3:11].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O>C(Cl)Cl>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][C@@H:18]1[C:23]([NH:9][NH:8][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=1)=[O:24])=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 1512538(3R)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 199167865-Fluoro-2-hydrazinylpyridine

Product 1

HCID 86687108(R)-3-[N'-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-morpholine-4-carboxylic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (143 mg, 1.13 mmol) in DCM (10.0 mL) was added (R)-morpholine-3,4-dicarboxylic acid 4-tert-butyl ester (260 mg, 1.13 mmol), EDC (238 mg, 1.24 mmol) and HOBt.H2O (15.0 mg, 0.11 mmol). The reaction was stirred overnight 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 (375 mg, 98%). LCMS (Method 1): Rt 2.69, m/z 341.2 [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-4519569dffda407da941fd37d62f9914
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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