Ethyl Acetate → 4-(6'-Chloro-3'-fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl ester

HRID 2066867Notes

Reaction equation

HRID 2066867 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[N:7][O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.[Cl:21][C:22]1[C:27]([CH2:28][OH:29])=[CH:26][C:25]([F:30])=[C:24](Cl)[N:23]=1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>CS(C)=O>[CH:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][CH:9]([O:8][N:7]=[C:4]2[CH2:3][CH2:2][N:1]([C:24]3[C:25]([F:30])=[CH:26][C:27]([CH2:28][OH:29])=[C:22]([Cl:21])[N:23]=3)[CH2:6][CH2:5]2)[CH2:14][CH2:13]1)=[O:16])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 23114857(2,6-Dichloro-5-fluoropyridin-3-yl)methanolHCID 57461147Isopropyl 4-(Piperidin-4-ylideneaminooxy)piperidine-1-carboxylate

Product 1

HCID 866550124-(6'-Chloro-3'-fluoro-5'-hydroxymethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-ylideneaminooxy)-piperidine-1-carboxylic acid isopropyl esterYield 30%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

2d (0.48 g, 1.7 mmol), 55a (0.36 g, 1.86 mmol) and diisopropylethylamine (0.31 mL, 1.9 mmol) were combined in 5 mL of DMSO and heated at 130° C. for 2 days. The mixture was cooled, poured into ethyl acetate (15 mL), washed with water (10 mL) and brine (10 mL), dried and concentrated. The residue was purified by flash chromatography (eluent: 10 to 50% ethyl acetate+0.1% triethylamine in hexane) to afford 55b as a yellow oil (0.22 g, 30% yield): LC-MS 425.1 (MH+).

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with water (10 mL) and brine (10 mL)
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (eluent: 10 to 50% ethyl acetate+0.1% triethylamine in hexane)

Sources & evidence

ORD record
ord-3bc81e21d38d4d1ea2c8ddbe09ff12c0
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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