Tetrahydrofuran → N-[4-((1R)-1-{[(R)-tert-Butylsulfinyl]amino}ethyl)-5-fluoro-2-methylphenyl]methanesulfonamide

HRID 1438393Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:13])=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.[CH3:14][C:15]([S@:18]([NH-:20])=[O:19])([CH3:17])[CH3:16].[BH4-].[Na+].[CH2:23]1COC[CH2:24]1>[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[C:15]([S@:18]([NH:20][C@@H:23]([C:3]1[C:2]([F:1])=[CH:7][C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])=[C:5]([CH3:13])[CH:4]=1)[CH3:24])=[O:19])([CH3:17])([CH3:16])[CH3:14]

Participants

Conditions

Temperature: 0 °C

Procedure

To a THF (5 ml) solution of the compound of Example 41 B (1.4 g, 5.5 mmol) and (R)-(+)-2-methyl-2-propanesulfinylamide (1.0 g, 8.26 mmol), titanium(IV) ethoxide (5.0 ml, 21.9 mmol) was added under a nitrogen atmosphere and the mixture was subjected to microwave irradiation at at 70° C. with stirring for 2.5 hours. After imine formation was confirmed with LC-MS (MS (ESI) m/z 347 (M−H)−, 349 (M+H)+), the mixture was cooled to 0° C. and sodium borohydride (707 mg, 18.7 mmol) was added and the reaction mixture was stirred for 2 hours at 0° C. The reaction mixture was partitioned with water and ethanol, then the mixture was stirred for 1 hour at room temperature. The mixture was filtrated through a Celite pad, and the filtrate was evaporated and concentrated in vacuo to give the title compound (1.9 g, 99%).

Workup

customirradiation at at 70° C.
stirringthe reaction mixture was stirred for 2 hours at 0° C
customThe reaction mixture was partitioned with water and ethanol
stirringthe mixture was stirred for 1 hour at room temperature
filtrationThe mixture was filtrated through a Celite pad
customthe filtrate was evaporated
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-21db8e950c784990b56ad1c93fae92a1
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622589B2

Reaction notes

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