Water → (E)-ethyl 3-(4-(4-(N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)-3,5-difluorophenyl)-2-methylacrylate

HRID 870182Notes

Reaction equation

HRID 870182 reaction equation
Cl[S:2]([C:5]1[CH:27]=[CH:26][C:8]([O:9][C:10]2[C:15]([F:16])=[CH:14][C:13](/[CH:17]=[C:18](\[CH3:24])/[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][C:11]=2[F:25])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[N:28]([CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][NH2:42])=[N+:29]=[N-:30].C(N(CC)CC)C.O>C(Cl)Cl>[N:28]([CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][NH:42][S:2]([C:5]1[CH:27]=[CH:26][C:8]([O:9][C:10]2[C:15]([F:16])=[CH:14][C:13](/[CH:17]=[C:18](\[CH3:24])/[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:12][C:11]=2[F:25])=[CH:7][CH:6]=1)(=[O:4])=[O:3])=[N+:29]=[N-:30]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 27352801-Amino-11-azido-3,6,9-trioxaundecaneHCID 86672338(E)-ethyl 3-(4-(4-(chlorosulfonyl)phenoxy)-3,5-difluorophenyl)-2-methylacrylate2×

Product 1

HCID 86672339(E)-ethyl 3-(4-(4-(N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)sulfamoyl)phenoxy)-3,5-difluorophenyl)-2-methylacrylateYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (E)-ethyl 3-(4-(4-(chlorosulfonyl)phenoxy)-3,5-difluorophenyl)-2-methylacrylate (intermediate 41.3) (250 mg, 0.60 mmol) in DCM (3 mL) was added a solution of 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethanamine (157 mg, 0.72 mmol) and triethylamine (72 mg, 0.72 mmol) in DCM (2 mL). After 15 minutes, water (10 mL) was added and the reaction mixture was extracted with DCM (2×25 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried (Na2SO4) and concentrated. The crude material was purified by flash chromatography on silica gel eluting with 50% EtOAc in DCM to give the title compound (169 mg).

Workup

  1. extractionthe reaction mixture was extracted with DCM (2×25 mL)
  2. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography on silica gel eluting with 50% EtOAc in DCM

Sources & evidence

ORD record
ord-c57c07ab7c6d4769beda63f6ffa102c1
Source dataset
uspto-grants-2015_03
Patent number
US08969377B2

Reaction notes

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