Dichloromethane → ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603413Notes

Reaction equation

HRID 603413 reaction equation
Br[C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]3)=[C:4]([O:28][CH3:29])[CH:3]=1.[S:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C(Cl)Cl.C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:29][O:28][C:4]1[CH:3]=[C:2]([C:32]2[CH:33]=[CH:34][S:30][CH:31]=2)[CH:27]=[CH:26][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]2

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 581760Thiophene-3-boronic acidHCID 59300414ethyl {(1S)-5-[3-(4-bromo-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate

Product 1

HCID 59300464ethyl ((1S)-5-{3-[2-methoxy-4-(3-thienyl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 59.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl {(1S)-5-[3-(4-bromo-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate (140 mg, 0.3 mmol) (Example 97), 3-thiopheneboronic acid (81.2 mg, 0.63 mmol), PdCl2(dppf).CH2Cl2 (90.5 mg, 0.07 mmol), and NaHCO3 (76.1 mg, 0.91 mmol) were suspended in DME (10 mL) and water (1 mL). The reaction mixture was degassed under vacuum for 3 min, and then purged with argon, after which the reaction mixture was agitated by orbital shaker at 80° C. for 24 h, and then at rt for 24 h. The reaction mixture was filtered through a pad of silica gel, and the filtrate was concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (EtOAc/hexanes (v/v)=1:9 to 1:1 gradient) to give 83 mg (59%) of the title compound as a yellow oil. 1H NMR (400 MHz, acetone-d6): δ 7.62-7.71 (m, 1H), 7.52-7.46 (m, 2H), 7.29 (d, 1H), 7.23-7.19 (m, 1H), 7.11-7.09 (m, 1H), 7.02-6.99 (m, 1H), 6.83-6.82 (m, 1H), 6.76-6.73 (m, 1H), 4.22-4.09 (m, 6H), 3.87 (s, 3H), 3.44 (m, 1H), 2.87-2.66 (m, 3H), 2.40-2.18 (m, 4H), 1.74-1.70 (m, 1H), 1.25 (t, 3H).

Workup

  1. customThe reaction mixture was degassed under vacuum for 3 min
  2. custompurged with argon
  3. waitat rt for 24 h
  4. filtrationThe reaction mixture was filtered through a pad of silica gel
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe crude material was purified by silica gel flash chromatography (EtOAc/hexanes (v/v)=1:9 to 1:1 gradient)

Sources & evidence

ORD record
ord-290d003658de4c0997932fa2559615c9
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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