Potassium Carbonate → 5-chloro-2-fluoro-N-(methylsulfonyl)-4-((5,6,7,8-tetrahydronaphthalen-2-yloxy)methyl)benzamide

HRID 1427909Notes

Reaction equation

Br[CH2:2][C:3]1[C:15]([Cl:16])=[CH:14][C:6]([C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8])=[C:5]([F:17])[CH:4]=1.[CH:18]1[C:27]2[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=2[CH:21]=[CH:20][C:19]=1[OH:28].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[Cl:16][C:15]1[C:3]([CH2:2][O:28][C:19]2[CH:20]=[CH:21][C:22]3[CH2:23][CH2:24][CH2:25][CH2:26][C:27]=3[CH:18]=2)=[CH:4][C:5]([F:17])=[C:6]([CH:14]=1)[C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 4-(bromomethyl)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide (40 mg, 0.12 mmol), 5,6,7,8-tetrahydronaphthalen-2-ol (40 mg, 0.24 mmol) and K2CO3 (60 mg, 0.24 mmol) in acetone (10 mL) was stirred at 50° C. for 4 h. The reaction was filtered and purified by reverse phase Combiflash (20%-50% MeCN in 0.1% formic acid) to give target compound (7.7 mg, 16%) as a white solid. LCMS (ESI) Method A: RT=4.12 min, m/z: 412.1 [M+H]+. 1H-NMR (400 MHz, MeOD-d4) δ 7.80 (d, J=6.0 Hz, 1H), 7.37 (d, J=5.6 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.74-6.68 (m, 2H), 5.11 (s, 2H), 3.20 (s, 3H), 2.74-2.70 (m, 4H), 1.80-1.77 (m, 4H).

Workup

filtrationThe reaction was filtered
custompurified by reverse phase Combiflash (20%-50% MeCN in 0.1% formic acid)

Sources & evidence

ORD record: ord-cfe37fb079c040e593852b8a2c3da02f
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933236B2

Reaction notes

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