Water → Methyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)-4-nitrobutanoate

HRID 511016Notes

Reaction equation

HRID 511016 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:12]([O:25][CH3:26])=[C:13](/[CH:19]=[CH:20]/[C:21]([O:23][CH3:24])=[O:22])[C:14]([CH3:18])=[C:15]([Cl:17])[CH:16]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].N12CCCN=C1CCCCC2.O.[N+:39]([CH3:42])([O-:41])=[O:40]>ClCCl>[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:12]([O:25][CH3:26])=[C:13]([CH:19]([CH2:42][N+:39]([O-:41])=[O:40])[CH2:20][C:21]([O:23][CH3:24])=[O:22])[C:14]([CH3:18])=[C:15]([Cl:17])[CH:16]=1)[CH3:10])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6375NitromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86666936Methyl (2E)-3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)acrylate

Product 1

HCID 86666937Methyl 3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)-4-nitrobutanoateYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl (2E)-3-(3-{1-[(tert-butoxycarbonyl)amino]ethyl}-5-chloro-2-methoxy-6-methylphenyl)acrylate (1.5 g, 3.9 mmol) in nitromethane (11 mL) at 0° C. was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (0.59 mL, 3.9 mmol) and allowed to warm to room temperature. The reaction mixture was heated at 60° C. for 21 h, cooled to room temperature, poured into water (100 ml) and extracted with EtOAc (2×75 mL). The organic layer was separated, washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to give a orange foam. The crude material was dissolved in dichloromethane and purified by flash column chromatography using EtOAc in hexanes (0%-30% over 30 min) to give the desired product (0.93 g, 53%) as a white foam. LCMS for C20H29ClN2O7Na (M+Na)+: m/z=467.2. Found: 467.1.

Workup

  1. temperatureThe reaction mixture was heated at 60° C. for 21 h
  2. temperaturecooled to room temperature
  3. extractionextracted with EtOAc (2×75 mL)
  4. customThe organic layer was separated
  5. washwashed with brine solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a orange foam
  10. custompurified by flash column chromatography
  11. customEtOAc in hexanes (0%-30% over 30 min)

Sources & evidence

ORD record
ord-1258b3a026a446368c00d2ab398b23c2
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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