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

Boron trichloride methylene chloride → 6-(N-(3-Chloro-4-hydroxyphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 2272346
Notes
Print preview

Reaction equation

HRID 2272346 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34]([NH:36][CH3:37])=[O:35])=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:11][C:10]=1[Cl:43])C1C=CC=CC=1.B(Cl)(Cl)Cl.C(Cl)Cl>C(Cl)Cl.CCOC(C)=O>[Cl:43][C:10]1[CH:11]=[C:12]([N:15]([C:20]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:23]3[C:24]([C:34]([NH:36][CH3:37])=[O:35])=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[O:26][C:22]=3[CH:21]=2)[S:16]([CH3:19])(=[O:18])=[O:17])[CH:13]=[CH:14][C:9]=1[OH:8]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 20463568Boron trichloride methylene chlorideHCID 1317322996-(N-(4-(Benzyloxy)-3-chlorophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Product 1

HCID 1317323006-(N-(3-Chloro-4-hydroxyphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 42.9%

Reagents, catalysts & solvents 2

HCID 6344
Dichloromethane
Solvent
HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6-(N-(4-(benzyloxy)-3-chlorophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.300 g, 0.485 mmol) in anhydrous DCM (12 mL) was cooled in an ice water bath and treated with 1M BCl3/DCM (2.00 mL, 2.00 mmol). After stirring in the ice bath for 10 minutes the solution was allowed to warm to RT. This solution was then combined with the solution from an analogous 50 mg scale reaction and poured into 50 mL of stirred ice water. The mixture was diluted with 50 mL of EtOAc, stirred vigorously for several minutes and the phases separated. The EtOAc solution was washed with water (2×), brine (1×), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude material was subjected to flash chromatography (silica gel, gradient from DCM to 1:1 DCM/EtOAc) followed by recrystallization from hexane/EtOAc to afford the title compound (0.110 g, 37%) as a white powder. Impure fractions from the above chromatography were combined, concentrated, and subjected to RP-HPLC purification (C18, MeCN/water/0.1% formic acid) to afford an additional portion of the title compound (0.107 g, 36%) for a total yield of 73%. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.45 (s, 1H) 8.40-8.48 (m, 1H) 8.18 (s, 1H) 7.90-8.01 (m, 2H) 7.61 (d, J=2.6 Hz, 1H) 7.34-7.45 (m, 3H) 7.14 (s, 1H) 6.96 (d, J=8.8 Hz, 1H) 3.30 (s, 3H) 2.82 (d, J=4.6 Hz, 3H) 2.20-2.34 (m, 1H) 0.77-1.09 (m, 3H) 0.43 (br. s., 1H). LCMS (m/z, ES+)=529 (M+H+).

Workup

  1. customThis solution was then combined with the solution from an analogous 50 mg scale reaction
  2. customthe phases separated
  3. washThe EtOAc solution was washed with water (2×), brine (1×)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to dryness at reduced pressure
  6. customfollowed by recrystallization from hexane/EtOAc

Sources & evidence

ORD record
ord-6380a24910ee4936904d68aedd543407
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09119868B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes