(Diethylamino)sulfur trifluoride → 1,8-Diethyl-1-(2-fluoroethyl)-1,3,4,9-tetrahydropyrano[3,4-b]indole
Reaction equation
[CH2:1]([C:3]1([CH2:18][CH2:19]O)[C:8]2[NH:9][C:10]3[C:15]([C:7]=2[CH2:6][CH2:5][O:4]1)=[CH:14][CH:13]=[CH:12][C:11]=3[CH2:16][CH3:17])[CH3:2].CCN(S(F)(F)[F:27])CC>C(Cl)Cl>[CH2:1]([C:3]1([CH2:18][CH2:19][F:27])[C:8]2[NH:9][C:10]3[C:15]([C:7]=2[CH2:6][CH2:5][O:4]1)=[CH:14][CH:13]=[CH:12][C:11]=3[CH2:16][CH3:17])[CH3:2]Participants
Procedure
To a stirred solution of compound 1 (136 mg, 0.5 mmol) in CH2Cl2 (2 mL) at −40° C. under argon, DAST (396 μL, 3.0 mmol, 6.0 eq) was slowly added in a dropwise manner. The resulting mixture was allowed to warm to room temperature and stirred for one hour before being cooled to 0° C. and quenched with MeOH (1 mL). The mixture was stirred an additional thirty minutes at room temperature, and then saturated NaHCO3 (10 mL) was added dropwise. The resulting aqueous layer was extracted three times with CH2Cl2. The combined organic phases were dried with Na2SO4, concentrated, and purified by column chromatography using 5:95:EtOAc:Hexane to give a yellow-white solid (45 mg, 33%): mp 118-119° C. 1HNMR (CDCl3, δ TMS): 0.88 (t, 3H), 1.37 (t, 3H), 1.94 (m, 2H), 2.29 (m, 2H), 2.78 (m, 2H), 2.86 (q, 2H), 3.99 (m, 2H), 4.57 (qq, 2H), 7.03-7.38 (m, 3H, Ar—H), 7.65 (br, 1H, NH). MS−: m/z 310 (MCl−), 274 ([M−H]−). Anal. (C17H22NOF): C, H, N.
Workup
- temperaturebefore being cooled to 0° C.
- customquenched with MeOH (1 mL)
- stirringThe mixture was stirred an additional thirty minutes at room temperature
- additionsaturated NaHCO3 (10 mL) was added dropwise
- extractionThe resulting aqueous layer was extracted three times with CH2Cl2
- dry with materialThe combined organic phases were dried with Na2SO4
- concentrationconcentrated
- custompurified by column chromatography
Sources & evidence
- ORD record
- ord-6dd42e9cf1ea41ada05987caf7dda2d2
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361680B2
Reaction notes
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