tert-Butylsulfinamide, (R)-(+)- → HCID 89612070, compound

HRID 2406271Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[CH:6]([O:12][CH3:13])[CH2:5]2.[C:14]([S@:18]([NH2:20])=[O:19])([CH3:17])([CH3:16])[CH3:15]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[N:20]\[S@@:18]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:19])/[C@@H:6]([O:12][CH3:13])[CH2:5]2

Participants

Conditions

Temperature: 68 °C

Procedure

A 22 L multi-neck reactor equipped with a condenser, a nitrogen inlet, a heating mantle and an overhead mechanical stirrer was charged with 5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-one (18) (622.88 g, 3.17 mol) and (R)-tert-butylsulfinamide (460.7 g, 3.8 mol). Tetrahydrofuran (3100 mL) was added to the mixture and the temperature dropped to 9° C. Ti(OEt)4 (985 mL, 4.76 mol) was added over 10 minutes. The mixture was heated to 68° C. and all solids dissolved at about 35° C. After 5 hours, the reaction achieved a 50% yield as determined by HPLC wt % assay. The reaction was stirred at 68° C. for an additional 5 hours until the undesired diastereomer decomposed to less than 5% (AUC). The reaction was cooled to ambient temperature over 2 hours and stirred for 16 hours. HPLC analysis indicated no obvious change in reaction profile during this period. This crude reaction mixture was taken in to the next step without further purification.

Workup

customA 22 L multi-neck reactor equipped with a condenser, a nitrogen inlet
additionthe temperature dropped to 9° C
dissolutionall solids dissolved at about 35° C
temperatureThe reaction was cooled to ambient temperature over 2 hours
stirringstirred for 16 hours
customin reaction profile during this period
customThis crude reaction mixture
customwas taken in to the next step without further purification

Sources & evidence

ORD record: ord-7deb9bc99fdd4d1f85e2e19a0d01bc49
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809356B2

Reaction notes

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