2-(T-Butyldimethylsilyloxy)-4-bromoanisole → 5-{[3-(Tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-hydroxy-methyl}-2-chloro-benzenesulfonamide

HRID 1810165Notes

Reaction equation

HRID 1810165 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([CH:15]=1)[O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].C([Li])(C)(C)C.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]=[O:31])=[CH:26][C:25]=1[S:32]([NH2:35])(=[O:34])=[O:33]>O1CCCC1>[C:11]([Si:8]([CH3:10])([CH3:9])[O:7][C:6]1[CH:15]=[C:2]([CH:30]([OH:31])[C:27]2[CH:28]=[CH:29][C:24]([Cl:23])=[C:25]([S:32]([NH2:35])(=[O:33])=[O:34])[CH:26]=2)[CH:3]=[CH:4][C:5]=1[O:16][CH3:17])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 109800492-(T-Butyldimethylsilyloxy)-4-bromoanisoleHCID 146546022-Chloro-5-formylbenzene-1-sulfonamideHCID 178418306HCID 178418306, compound

Product 1

HCID 581074595-{[3-(Tert-butyl-dimethyl-silanyloxy)-4-methoxy-phenyl]-hydroxy-methyl}-2-chloro-benzenesulfonamideYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (5-bromo-2-methoxy-phenoxy)-tert-butyl-dimethyl-silane (2 g, 6.32 mmol) dissolved in tetrahydrofuran (25 mL) at −78° C. under nitrogen is dropwisely added 1.7 M of tert-butyllithium (8.06 mL, 12.6 mmol). The reaction mixture is stirred at −78° C. for 5 minutes Then, the solution of 2-chloro-5-formyl-benzenesulfonamide (0.462 g, 2.11 mmol) in tetrahydrofuran (5 mL) is added slowly. The reaction mixture is warmed up to room temperature and stirred for 24 h. The reaction is quenched with 1 N of HCl, and extracted with ethyl acetate three times. The combined organic extracts are washed with a saturated sodium chloride solution, dried with magnesium sulfate, and concentrated in vacuo. Purification by silica gel chromatography (50% ethyl acetate-hexane) provides 0.57 g (59%) of the title compound as a brown oil. 1H NMR (CDCl3): δ 8.00 (m, 1H), 7.40 (m, 2H), 6.70 (d, 3H), 5.70 (s, 1H), 5.00 (m, 2H), 3.70 (s, 3H), 0.90 (s, 9H), 0.05 (s, 6H).

Workup

  1. temperatureThe reaction mixture is warmed up to room temperature
  2. stirringstirred for 24 h
  3. customThe reaction is quenched with 1 N of HCl
  4. extractionextracted with ethyl acetate three times
  5. washThe combined organic extracts are washed with a saturated sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography (50% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-9f793d8c2b2a4a188e2c7a88625307e4
Source dataset
uspto-grants-2013_01
Patent number
US08362063B2

Reaction notes

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