Dichloromethane → Tert-butyl {(3r)-1-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-2-formylphenyl]pyrrolidin-3-yl}carbamate

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	2-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trione	HCID 21878638	—
Reactant	Tert-butyl {(3r)-1-[2-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidin-3-yl}carbamate	HCID 58746884	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	Tert-butyl {(3r)-1-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-2-formylphenyl]pyrrolidin-3-yl}carbamate	HCID 58746896	73%

Reaction Conditions

Temperature	80 °C

Reaction Steps

Boronic ester 22-B in dioxane (1 mL) was treated with potassium carbonate (124 mg, 0.901 mmol), heterocycle 9-A (48 mg, 0.21 mmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (17.6 mg, 0.0216 mmol). The solution was degassed, placed under nitrogen and heated to 80° C. for 48 hours. The solution was allowed to cool to ambient temperature, diluted with ethyl acetate (10 mL) and washed with water (10 mL). The organics were separated, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (30 ethyl acetate/hexanes) to afford a yellow solid 22-C (63 mg, 73%). 1H NMR (500 MHz, CD3OD): δ 10.05 (s, 1H), 8.25 (d, J=1.95 Hz, 1H), 7.87 (dd, J=11.22 Hz, 1H), 7.06 (d, J=9.27 Hz, 1H), 6.84 (s, 1H), 4.24 (m, 1H), 3.70 (m, 2H), 3.65 (m, 1H), 3.19 (m, 1H), 2.28 (m, 1H), 2.26 (m, 1H), 1.72 (s, 9H), 1.46 (s, 9H); LCMS found for C23H31N3O6S (M+H)+: m/z=478.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07141596B2
Source dataset	uspto-grants-2006_11
ORD ID	ord-149e77a9b02f4303aa9d4008cbe1426f
Source note	uspto-grants-2006_11