Potassium Phosphate, Tribasic → 4-(2-Fluoro-4-trimethylsilanyl-phenylamino)-benzo[d]isothiazole-5-carboxylic acid tert-butyl ester

HRID 79028Notes

Reaction equation

HRID 79028 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([Si:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[NH2:12].[C:13]([O:17][C:18]([C:20]1[CH:21]=[CH:22][C:23]2[S:27][N:26]=[CH:25][C:24]=2[C:28]=1Br)=[O:19])([CH3:16])([CH3:15])[CH3:14].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:13]([O:17][C:18]([C:20]1[CH:21]=[CH:22][C:23]2[S:27][N:26]=[CH:25][C:24]=2[C:28]=1[NH:12][C:3]1[CH:4]=[CH:5][C:6]([Si:8]([CH3:9])([CH3:11])[CH3:10])=[CH:7][C:2]=1[F:1])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58374343Tert-butyl 4-bromobenzo[d]isothiazole-5-carboxylateHCID 595965992-Fluoro-4-(trimethylsilyl)aniline

Product 1

HCID 670835784-(2-Fluoro-4-trimethylsilanyl-phenylamino)-benzo[d]isothiazole-5-carboxylic acid tert-butyl esterYield 78.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2-fluoro-4-trimethylsilanyl-phenylamine (340 mg, 1.43 mmol), 4-bromo-benzo[d]isothiazole-5-carboxylic acid tert-butyl ester (449 mg, 1.43 mmol), Pd2 dba3 (65 mg, 0.07 mmol), Xantphos (83 mg, 0.14 mmol) and potassium phosphate tribasic (455 mg, 2.14 mmol) in toluene (5 mL) was degassed and then the reaction mixture heated at 90° C. for 18 hours. The cooled reaction mixture was diluted with ethyl acetate, filtered through Celite®, and the filtrate concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 2.5 to 5% diethyl ether in pentane) to give the title compound as a dark oil (465 mg, 78%). LCMS (Method B): RT=5.76 min, [M+H]+=417.

Workup

  1. customThe cooled reaction mixture
  2. filtrationfiltered through Celite®
  3. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-08870ac8b2754831847f6c1f3cdc3533
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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