2,6-Lutidine → 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluoro-N-((2-hydroxyethyl)-sulfonyl)benzamide

HRID 1849557Notes

Reaction equation

HRID 1849557 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:28]([CH:29]4[CH2:31][CH2:30]4)=[CH:27][C:16]([C:17]([NH:19][S:20]([CH2:23][CH2:24][O:25]C)(=[O:22])=[O:21])=[O:18])=[C:15]([F:32])[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.B(Br)(Br)Br.N1C(C)=CC=CC=1C>C(Cl)Cl>[C:1]12([CH2:11][O:12][C:13]3[C:28]([CH:29]4[CH2:30][CH2:31]4)=[CH:27][C:16]([C:17]([NH:19][S:20]([CH2:23][CH2:24][OH:25])(=[O:22])=[O:21])=[O:18])=[C:15]([F:32])[CH:14]=3)[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 25134Boron tribromideHCID 867029024-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluoro-N-((2-methoxyethyl)sulfonyl)benzamide

Product 1

HCID 867029014-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluoro-N-((2-hydroxyethyl)-sulfonyl)benzamideYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) stirred solution of 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluoro-N-((2-methoxyethyl)sulfonyl)benzamide (0.30 g, 0.64 mmol) in methylene chloride (6 mL) was added a solution of boron tribromide (0.12 mL, 1.29 mmol) and 2,6-lutidine (0.15 mL, 1.29 mmol) in methylene chloride (1 mL) dropwise. The reaction mixture was stirred at 0° C. for 2 h and at ambient temperature for 1 h, then cooled to 0° C. and quenched with saturated sodium bicarbonate solution (15 mL). The mixture was diluted with methylene chloride (15 mL), layers were separated, and the aqueous layer was extracted with methylene chloride (2×15 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 10% to 75% gradient of ethyl acetate in hexanes to afford the title compound as colorless solid (0.07 g, 25%): 1H NMR (300 MHz, CDCl3) δ 8.71 (br. s, 1H), 7.64-7.52 (m, 1H), 6.64-6.50 (m, 1H), 4.22-4.07 (m, 2H), 3.86-3.74 (m, 2H), 3.56 (s, 2H), 2.57 (s, 1H), 2.09-1.99 (m, 4H), 1.84-1.63 (m, 12H), 1.00-0.89 (m, 2H), 0.69-0.59 (m, 2H); MS (ES+) m/z 452.3 (M+1).

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with saturated sodium bicarbonate solution (15 mL)
  3. additionThe mixture was diluted with methylene chloride (15 mL), layers
  4. customwere separated
  5. extractionthe aqueous layer was extracted with methylene chloride (2×15 mL)
  6. washThe combined organic layers were washed with brine (20 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography
  11. washeluting with a 10% to 75% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-9b78ede7d10d456eac47551fb8d8228c
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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