Hydrochloric Acid → tert-butyl 6-hydroxy-8-phenylsulfonyl-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

HRID 2179347Notes

Reaction equation

HRID 2179347 reaction equation
Cl[C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:3]=1.[OH-:31].[K+].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl>O.O1CCOCC1>[OH:31][C:2]1[C:7]2[O:8][C:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C:10]=3[C:6]=2[CH:5]=[C:4]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 68109641tert-butyl 6-chloro-8-phenylsulfonyl-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

Product 1

HCID 68108520tert-butyl 6-hydroxy-8-phenylsulfonyl-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylateYield 34.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of the product of Example 44, step C (1.41 g, 3.14 mmol), di-palladium-tris(dibenzylideneacetone) (575 mg, 0.62 mmol), potassium hydroxide (387 mg, 6.91 mmol) and 2-(di-tert-butylphosphino)-2′,4′,6′-triisopropyl-3,4,5,6-tetramethyl-1,1′-biphenyl (121 mg, 0.25 mmol) in water (14 mL) and 1,4-dioxane (14 mL) was heated to 110° C. for 24 h. After cooling to ambient temperature, the reaction mixture was neutralized with 1N aqueous HCl, filtered through celite bed and extracted with ethyl acetate (4×30 mL). The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product which was purified by column chromatography (SiO2, 7:3 hexanes/ethyl acetate) providing tert-butyl 6-hydroxy-8-phenylsulfonyl-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (470 mg, 34%): 1H NMR (CDCl3, 300 MHz) δ 7.93-7.90 (m, 2H), 7.62 (br s, 1H), 7.55-7.43 (m, 3H), 7.39 (d, J=1.8 Hz, 1H), 4.54 (s, 2H), 3.81 (t, J=5.4 Hz, 2H), 2.83 (t, J=5.7 Hz, 2H), 1.51 (s, 9H).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. filtrationfiltered through celite bed
  3. extractionextracted with ethyl acetate (4×30 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto give the crude product which
  8. customwas purified by column chromatography (SiO2, 7:3 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d874a6bde83b44de881621c9f584c1a4
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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