Cesium carbonate → tert-butyl 8-(3-fluorophenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate

HRID 2179311Notes

Reaction equation

HRID 2179311 reaction equation
Br[C:2]1[CH:3]=[CH:4][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.[F:22][C:23]1[CH:24]=[C:25]([S:29]([O-:31])=[O:30])[CH:26]=[CH:27][CH:28]=1.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+].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>C1(C)C=CC=CC=1>[F:22][C:23]1[CH:24]=[C:25]([S:29]([C:2]2[CH:3]=[CH:4][C:5]3[O:14][C:13]4[CH2:12][CH2:11][N:10]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C:8]=4[C:6]=3[CH:7]=2)(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23717246Sodium 3-fluorobenzene-1-sulfinateHCID 68109313HCID 68109313, compound

Product 1

HCID 68108458tert-butyl 8-(3-fluorophenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylateYield 37%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of product of step B (300 mg, 0.85 mmol), sodium 3-fluorobenzenesulfinate (186 mg, 1.02 mmol), di-palladium-tris(dibenzylideneacetone) (78 mg, 0.08 mmol), cesium carbonate (416 mg, 1.28 mmol) and xantphos (99 mg, 0.17 mmol) was suspended in anhydrous toluene (4.5 mL). The reaction flask was purged with argon, sealed and heated to 120° C. for 14 h. The reaction mixture was cooled to ambient temperature, diluted with dichloromethane and filtered through a celite bed. The filtrate was concentrated in vacuo to give the crude product which was purified by flash column chromatography (SiO2, 3:2 hexanes/ethyl acetate) providing tert-butyl 8-(3-fluorophenylsulfonyl)-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (135 mg, 37%) as a pale yellow solid: 1H NMR (CDCl3, 300 MHz) δ 8.08 (s, 1H), 7.83 (dd, J=8.7, 1.8 Hz, 1H), 7.77-7.72 (m, 1H), 7.65 (dt, J=7.8, 2.1 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.51-7.44 (m, 1H), 7.25-7.20 (m, 1H), 4.58 (s, 2H), 3.84 (t, J=5.4 Hz, 2H), 2.91-2.84 (m, 2H), 1.55 (s, 9H).

Workup

  1. customThe reaction flask was purged with argon
  2. customsealed
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. additiondiluted with dichloromethane
  5. filtrationfiltered through a celite bed
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give the crude product which
  8. customwas purified by flash column chromatography (SiO2, 3:2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-b5faf69c089e4b179b1e2710bc85bb54
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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