Trifluoroacetic acid → HCID 68109660, compound

HRID 2179370Notes

Reaction equation

HRID 2179370 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([C:8]2(O)[CH2:12][CH2:11][O:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[K+].[K+]>ClCCl>[I:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][CH2:11][O:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 68108894HCID 68108894, compound

Product 1

HCID 68109660HCID 68109660, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the product of step A (2.0 g, 3.79 mmol) in dichloromethane (15 mL) was cooled to 0° C. under a nitrogen atmosphere before addition of triethylsilane (5.0 mL, 31.38 mmol), TFA (4.4 mL, 55.74 mmol) and borontrifluoride-diethyletherate complex (7.0 mL, 55.74 mmol). The reaction mixture was stirred for 48 h at ambient temperature, then poured into K2CO3 (aq.) solution and extracted with dichloromethane. The combined organic layer was dried over Na2SO4, concentrated and the residue purified by flash column chromatography (SiO2, 98:2 hexanes/ethyl acetate) to give 3-(3-iodophenyl)tetrahydrofuran (0.89 g, 86%) as a colorless liquid: 1H NMR (CDCl3, 300 MHz) δ 7.60 (t, J=1.8 Hz, 1H), 7.56 (td, J=7.8 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 7.04 (t, J=7.8 Hz, 1H), 4.15-4.00 (m, 2H), 3.96-3.84 (m, 1H), 3.76-3.66 (m, 1H), 3.33 (p, J=7.8 Hz, 1H), 2.43-2.29 (m, 1H), 2.04-1.89 (m, 1H). Step C: The product of step B was coupled with lithium 2-(tert-butoxycarbonyl)-6-chloro-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine-8-sulfinate following the procedure of Example 50, step A. The crude product was purified by flash column chromatography (SiO2, 4:1 hexanes/ethyl acetate) to give tert-butyl 6-chloro-8-(3-(tetrahydrofuran-3-yl)phenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (55 mg, 8%) as an off-white solid: 1H NMR (CDCl3, 300 MHz) δ 8.02-7.91 (m, 1H), 7.87-7.76 (m, 3H), 7.51-7.44 (m, 2H), 4.57 (s, 2H), 4.18-4.02 (m, 2H), 3.97-3.78 (m, 3H), 3.77-3.67 (m, 1H), 3.46 (p, J=7.5 Hz, 1H), 2.98-2.84 (m, 2H), 2.49-2.34 (m, 1H), 2.06-1.89 (m, 1H), 1.50 (s, 9H); APCI MS m/z 418 [(M+H)—C5H9O2]+.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customthe residue purified by flash column chromatography (SiO2, 98:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-55c31556ff77441cb5a56ac25578c60c
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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