1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-(tert-butoxycarbonylamino)-2-fluorobenzoate

HRID 1529528Notes

Reaction equation

HRID 1529528 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[C:11]([F:18])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:21]=[N+:22]([O-:40])[CH:23]=[C:24]([Cl:39])[C:25]=1[CH2:26][C@@H:27]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1)O.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C1C=CN=CC=1>[Cl:39][C:24]1[CH:23]=[N+:22]([O-:40])[CH:21]=[C:20]([Cl:19])[C:25]=1[CH2:26][C@H:27]([O:14][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[CH:10][C:11]=1[F:18])[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 71092494(S)-3,5-dichloro-4-(2-(3,4-dimethoxyphenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 834102094-((tert-Butoxycarbonyl)amino)-2-fluorobenzoic acid

Product 1

HCID 86720691[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]-4-(tert-butoxycarbonylamino)-2-fluorobenzoateYield 77.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(tert-butoxycarbonylamino)-2-fluorobenzoic acid (0.200 g, 0.78 mmol) and (1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethanol (0.270 g, 0.78 mmol) in dichloromethane (10.0 mL) was added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (0.300 g, 1.57 mmol) and N,N-dimethylpyridin-4-amine (0.048 g, 0.39 mmol). The reaction was stirred at room temperature for 16 hours. The reaction was quenched by addition of saturated aqueous sodium bicarbonate solution (25.0 mL) and extracted with dichloromethane (×2). The combined organic extracts were dried on magnesium sulphate, filtered, and the solvent removed in vacuo to afford a yellow oil. The crude material was purified by silica gel chromatography eluting sequentially with iso-hexane and 10% methanol in ethyl acetate to afford the title compound as a yellow solid (0.351 g, 77%).

Workup

  1. customThe reaction was quenched by addition of saturated aqueous sodium bicarbonate solution (25.0 mL)
  2. extractionextracted with dichloromethane (×2)
  3. customThe combined organic extracts were dried on magnesium sulphate
  4. filtrationfiltered
  5. customthe solvent removed in vacuo
  6. customto afford a yellow oil
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting sequentially with iso-hexane and 10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-68c4271a7f374280b886075eabc9e100
Source dataset
uspto-grants-2015_07
Patent number
US09090606B2

Reaction notes

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