Acetaldehyde → 4-(adamantan-1-ylmethoxy)-2-fluoro-N-((2-hydroxypropyl)sulfonyl)-benzamide

HRID 1849748Notes

Reaction equation

HRID 1849748 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:25](Br)=[CH:24][C:16]([C:17]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C([Li])(C)(C)C.[CH:33](=[O:35])[CH3:34]>O1CCCC1>[C:1]12([CH2:11][O:12][C:13]3[CH:25]=[CH:24][C:16]([C:17]([NH:19][S:20]([CH2:23][CH:33]([OH:35])[CH3:34])(=[O:22])=[O:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

5

Reactant 3

HCID 177AcetaldehydeHCID 867036294-(adamantan-1-ylmethoxy)-5-bromo-2-fluoro-N-(methylsulfonyl)benzamideHCID 178418306HCID 178418306, compound

Product 1

HCID 867036304-(adamantan-1-ylmethoxy)-2-fluoro-N-((2-hydroxypropyl)sulfonyl)-benzamideYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-(adamantan-1-ylmethoxy)-5-bromo-2-fluoro-N-(methylsulfonyl)benzamide (0.340 g, 0.74 mmol) in anhydrous tetrahydrofuran (5 mL) was added tert-butyllithium (1.7 M solution in pentane, 1.31 mL, 2.22 mmol) at −78° C. The reaction mixture was stirred for 30 minutes at −78° C. followed by addition of acetaldehyde (0.21 mL, 3.70 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 16 hours. After quenched with 1 N hydrochloric acid (5 mL), the mixture was diluted with ethyl acetate (100 mL). The organic phase was washed with brine (5 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate gave a residue which was purified by reverse-phase preparative HPLC to afford the title compound as an off-white solid (0.075 g, 24%): 1H NMR (300 MHz, DMSO-d6) δ 11.79 (s, 1H), 7.60 (t, J=8.7 Hz, 1H), 6.93 (dd, J=13.0, 2.2 Hz, 1H), 6.86 (dd, J=8.7, 2.3 Hz, 1H), 5.04 (br s, 1H), 4.17-4.07 (m, 1H), 3.65-3.56 (m, 1H), 3.63 (s, 2H), 3.45 (dd, J=14.3, 5.1 Hz, 1H), 2.02-1.94 (m, 3H), 1.76-1.57 (m, 12H), 1.20 (d, J=6.3 Hz, 3H); MS (ES−) m/z 424.2 (M−1).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 16 hours
  3. customAfter quenched with 1 N hydrochloric acid (5 mL)
  4. additionthe mixture was diluted with ethyl acetate (100 mL)
  5. washThe organic phase was washed with brine (5 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customConcentration of the filtrate gave a residue which
  9. customwas purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-6fa39a0c71274920886a15360518f593
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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