Triethylamine → 4-[6-(2-Chloro-4-fluoro-benzoylamino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1822042Notes

Reaction equation

HRID 1822042 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[N:16]=2)[CH2:10][CH:9]1[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:23][C:24]1[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:25]=1[C:26](Cl)=[O:27].C(N(CC)CC)C.O1CCOCC1>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:26](=[O:27])[C:25]3[CH:29]=[CH:30][C:31]([F:33])=[CH:32][C:24]=3[Cl:23])[N:16]=2)[CH2:10][CH:9]1[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 312751,4-DioxaneHCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 690712164-(6-Amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 690663474-[6-(2-Chloro-4-fluoro-benzoylamino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 4-(6-amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester cis isomer 1 (preparation 63, 0.025 g, 0.08 mmol), 2-chloro-4-fluoro-benzoyl chloride (0.10 g, 0.52 mmol), triethylamine (0.10 mL, 0.69 mmol) and 1,4-dioxane (10 mL), stir and heat to reflux. After 3 hr., cool to ambient temperature, dilute with methanol (10 mL) and load on an SCX column (10 g). Wash with methanol (2×25 mL). Elute product with 2M ammonia/methanol (2×25 mL). Eluent concentrated to give crude title compound. Mass spectrum (electrospray): m/z=364.1 (M+1-100) loss of t-BOC from parent. Use without further characterization in next step.

Workup

  1. temperatureheat to reflux
  2. washWash with methanol (2×25 mL)
  3. concentrationEluent concentrated

Sources & evidence

ORD record
ord-189b6ead0288427babf6d8f9aa12e369
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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