Thiophenol → tert-butyl 6-chloro-8-(phenylthio)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

HRID 2179433Notes

Reaction equation

HRID 2179433 reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:22])[C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=1.[C:23]1([SH:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:22][C:4]1[C:5]2[O:14][C:13]3[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=3[C:6]=2[CH:7]=[C:2]([S:29][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 7969ThiophenolHCID 81531DiisopropylethylamineHCID 68109024tert-butyl 6-chloro-8-bromo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

Product 1

HCID 68109020tert-butyl 6-chloro-8-(phenylthio)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylateYield 102.5%

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of tert-butyl 8-bromo-6-chloro-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (1.00 g, 2.58 mmol), benzenethiol (0.40 mL, 3.87 mmol), di-palladium-tris(dibenzylideneacetone) (118 mg, 0.13 mmol), N,N-diisopropylethylamine (0.9 mL, 5.16 mmol) and xantphos (149 mg, 0.26 mmol) were suspended in anhydrous dioxane (10 mL). The reaction flask was purged with argon and the mixture heated to 110° C. for 14 h. After cooling, the reaction mixture was diluted with dichloromethane and filtered through a celite bed. The filtrate was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 9:1 hexanes/ethyl acetate) to give tert-butyl 6-chloro-8-(phenylthio)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (1.10 g, 91%) as an off-white solid: 1H NMR (CDCl3, 400 MHz) δ 7.47-7.38 (m, 1H), 7.34 (d, J=1.2 Hz, 1H), 7.31-7.27 (m, 1H), 7.26-7.25 (m, 2H), 7.24-7.19 (m, 2H), 4.50 (s, 2H), 3.86-3.79 (m, 2H), 2.92-2.87 (m, 2H), 1.50 (s, 9H).

Workup

  1. customThe reaction flask was purged with argon
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with dichloromethane
  4. filtrationfiltered through a celite bed
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue purified by flash column chromatography (SiO2, 9:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7e98050595504faea56a45abb9405867
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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