Ethanol → ethyl 2-(tert-butoxy)-2-[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-5-phenylthiophen-2-yl]acetate

HRID 590988Notes

Reaction equation

HRID 590988 reaction equation
Br[C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[CH:13]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:14]([O:16][CH2:17][CH3:18])=[O:15].CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]3[C:39](=[CH:40][CH:41]=2)[O:38][CH2:37][CH2:36][CH2:35]3)O1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].O>[C:20]([O:19][CH:13]([C:3]1[S:4][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:6][C:2]=1[C:32]1[CH:41]=[CH:40][C:39]2[O:38][CH2:37][CH2:36][CH2:35][C:34]=2[CH:33]=1)[C:14]([O:16][CH2:17][CH3:18])=[O:15])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 438110342-(3,4-dihydro-2H-1-benzopyran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 70819430Ethyl 2-(3-bromo-5-phenylthiophen-2-yl)-2-(tert-butoxy)acetate

Product 1

HCID 70855383ethyl 2-(tert-butoxy)-2-[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-5-phenylthiophen-2-yl]acetateYield 82%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A solution of ethyl 2-(3-bromo-5-phenylthiophen-2-yl)-2-(tert-butoxy)acetate (10d) (86 mg, 0.22 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (101 mg, 0.39 mmol) and sodium carbonate (92 mg, 0.87 mmol) in a mixture of toluene (1.26 mL), ethanol (0.6 mL) and water (0.5 mL) was bubbled with nitrogen for 5 minutes. Palladium tetrakis(triphenylphosphine) (12 mg, 0.01 mmol) was added and the reaction mixture was heated at 95° C. overnight. After cooling to room temperature, water (2 mL) was added. The aqueous layer was extracted with toluene (2×8 mL). The organic layers were washed with brine (5 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20) to provide the desired product (10e) (80 mg, 0.18 mmol, 82%).

Workup

  1. customwas bubbled with nitrogen for 5 minutes
  2. temperatureAfter cooling to room temperature
  3. extractionThe aqueous layer was extracted with toluene (2×8 mL)
  4. washThe organic layers were washed with brine (5 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 80/20)

Sources & evidence

ORD record
ord-a6d6aaf81e404f3f9c1850989bb6cfde
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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