Diisopropylethylamine → benzyl 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)-N-(3-(4-methoxyphenoxy)propylsulfonyl)propylsulfonamido)benzoate

HRID 1943949Notes

Reaction equation

HRID 1943949 reaction equation
[NH2:1][C:2]1[C:3]([F:19])=[C:4]([C:15]([Cl:18])=[CH:16][CH:17]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].[CH3:20][O:21][C:22]1[CH:35]=[CH:34][C:25]([O:26][CH2:27][CH2:28][CH2:29][S:30](Cl)(=[O:32])=[O:31])=[CH:24][CH:23]=1.C(N([CH:42]([CH3:44])[CH3:43])C(C)C)C>C(Cl)Cl>[Cl:18][C:15]1[C:4]([C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])=[C:3]([F:19])[C:2]([N:1]([S:30]([CH2:29][CH2:28][CH2:27][O:26][C:43]2[CH:42]=[CH:44][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)(=[O:32])=[O:31])[S:30]([CH2:29][CH2:28][CH2:27][O:26][C:25]2[CH:34]=[CH:35][C:22]([O:21][CH3:20])=[CH:23][CH:24]=2)(=[O:32])=[O:31])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 51420933-(4-Methoxyphenoxy)propane-1-sulfonyl chlorideHCID 58087305Benzyl 3-amino-6-chloro-2-fluorobenzoate

Product 1

HCID 131730287benzyl 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)-N-(3-(4-methoxyphenoxy)propylsulfonyl)propylsulfonamido)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A 100 mL, round-bottomed flask was charged with benzyl 3-amino-6-chloro-2-fluorobenzoate (1.0 g, 3.58 mmol), 3-(4-methoxyphenoxy)propane-1-sulfonyl chloride (2.84 g, 10.7 mmol), N-ethyl-N-isopropylpropan-2-amine (1.91 mL, 10.7 mmol) and DCM (15 mL). The reaction mixture was stirred at −78° C. until LC-MS showed that the starting material had been consumed (about 12 hours). Then the reaction mixture was cooled to room temperature and partitioned between EtOAc (500 mL) and water (200 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (3×200 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield crude benzyl 6-chloro-2-fluoro-3-(3-(4-methoxyphenoxy)-N-(3-(4-methoxyphenoxy)propylsulfonyl)propylsulfonamido)benzoate. The crude product was used in the next step.

Workup

  1. customhad been consumed (about 12 hours)
  2. temperatureThen the reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc (500 mL) and water (200 mL)
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×200 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-f2dde63bae6f46b197ac9d77977941e6
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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