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

HRID 1822043Notes

Reaction equation

HRID 1822043 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].C(N(CC)CC)C.[Cl:30][C:31]1[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[C:32]=1[C:33](Cl)=[O:34]>O1CCOCC1>[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:33](=[O:34])[C:32]3[C:36]([F:40])=[CH:37][CH:38]=[CH:39][C:31]=3[Cl:30])[N:16]=2)[CH2:10][CH:9]1[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27365472-Chloro-6-fluorobenzoyl chlorideHCID 690712164-(6-Amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 690729454-[6-(2-Chloro-6-fluoro-benzoylamino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine 4-(6-Amino-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester cis isomer 1 (preparation 63, 0.286 g, 0.93 mmol), 1,4-dioxane (10 mL), triethylamine (0.16 mL, 1.12 mmol) and 2-chloro-6-fluorobenzoyl chloride (0.215 g, 1.12 mmol) with stirring at ambient temperature. After 2 hr., partition between water (50 mL) and 4:1 hexane:ethyl acetate (100 mL). Separate aqueous layer and wash with 4:1 hexane:ethyl acetate (50 mL). Combine organic layers, dry over sodium sulfate, filter and concentrate to obtain the title compound (0.53 g>100%). Mass spectrum (electrospray): m/z=462.3 (M−1); 1H NMR (CDCl3): 7.9 (m, 2H), 7.65 (dd, 1H), 7.4 (m, 1H), 7.25 (m, 1H), 7.1 (dd, 1H), 6.5 (d, 1H), 5.25 (m, 1H), 4.35 (m, 1H), 3.9 (m, 1H), 3.25 (m, 1H), 1.9 (m, 3H), 1.7 (m, 1H), 1.45 (s, 9H), 1.3 (d, 3H).

Workup

  1. custom, partition between water (50 mL) and 4:1 hexane
  2. washSeparate aqueous layer and wash with 4:1 hexane
  3. dry with materialCombine organic layers, dry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-8c5b1007e3f44baa90a374f9bc64e6ea
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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