HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Toluene → Methyl 3-(Boc-amino)-2-(4-chlorophenyl)propanoate

HRID 1675888
Notes
Print preview

Reaction equation

HRID 1675888 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:13]C(OC(C)(C)C)=O)[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[C:21]([OH:27])(C(F)(F)F)=[O:22].C1(P([N:42]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.[N-]=[N+]=[N-].[C:55]1([CH3:61])[CH:60]=CC=C[CH:56]=1>C(Cl)Cl.C(O)(C)(C)C.Cl[Sn](Cl)(Cl)Cl>[C:55]([O:27][C:21]([NH:42][CH2:13][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[C:9]([O:11][CH3:12])=[O:10])=[O:22])([CH3:61])([CH3:60])[CH3:56]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 6

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 33558AzideHCID 199401P,P-Diphenylphosphinic azideHCID 666183864-Tert-butyl 1-methyl 2-(4-chlorophenyl)succinate

Product 1

HCID 66617917
Methyl 3-(Boc-amino)-2-(4-chlorophenyl)propanoate
Yield 79%

Reagents, catalysts & solvents 3

HCID 24287Tin tetrachlorideCatalystHCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-tert-butyl 1-methyl 2-(4-chlorophenyl)succinate (14.3 g, 47.7 mmol) in DCM (75 mL) was treated with neat TFA (75 mL) at room temperature. The mixture was stirred for five hours to completion, after which the reaction mixture was concentrated and dried in vacuo overnight to afford a white solid. The solid was suspended in toluene (160 mL), cooled to 0° C., and treated successively with diphenylphosphoryl azide (11.2 mL, 52.1 mmol) and triethylamine (13.2 mL, 94.7 mmol). The reaction mixture (homogeneous) was allowed to warm to room temperature and stirred for four hours to completion. The solution was quenched with 1% citric acid solution and extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a light brown oil. The crude azide was dissolved in tert-butanol (160 mL), treated with neat SnCl4 (1.0M solution, 2.37 mL, 2.37 mmol), and carefully heated to 90° C. with evolution of nitrogen. The mixture was stirred at 90° C. for 2.5 hours and cooled to room temperature. The solution was quenched with saturated NaHCO3 solution and then concentrated. The oily mixture was extracted with EtOAc (3×), and the combined organics were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by on silica gel (4:1 hexanes:EtOAc) to afford the methyl 3-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)propanoate as a pale yellow oil (11.7 g, 79%). 1H NMR (CDCl3, 400 MHz) δ 7.31 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 4.86 (br s, 1H), 3.88 (m, 1H), 3.69 (s, 3H), 3.58 (m, 1H), 3.49 (m, 1H), 1.42 (s, 9H).

Workup

  1. concentrationafter which the reaction mixture was concentrated
  2. customdried in vacuo overnight
  3. customto afford a white solid
  4. temperatureto warm to room temperature
  5. stirringstirred for four hours to completion
  6. customThe solution was quenched with 1% citric acid solution
  7. extractionextracted with EtOAc (3×)
  8. washThe combined organics were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give a light brown oil
  13. temperaturecarefully heated to 90° C. with evolution of nitrogen
  14. stirringThe mixture was stirred at 90° C. for 2.5 hours
  15. temperaturecooled to room temperature
  16. customThe solution was quenched with saturated NaHCO3 solution
  17. concentrationconcentrated
  18. extractionThe oily mixture was extracted with EtOAc (3×)
  19. washthe combined organics were washed with brine
  20. dry with materialdried over MgSO4
  21. filtrationfiltered
  22. concentrationconcentrated in vacuo
  23. customThe residue was purified by on silica gel (4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-3c7b41ff35d3498aa270035112b756e4
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08003651B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes