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

HRID 590995Notes

Reaction equation

HRID 590995 reaction equation
Br[C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:5][C:6]=1[CH:7]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([O:10][CH3:11])=[O:9].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[C:33]3[C:38](=[CH:39][CH:40]=2)[O:37][CH2:36][CH2:35][CH2:34]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:13]([O:12][CH:7]([C:6]1[CH:5]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:3][C:2]=1[C:31]1[CH:40]=[CH:39][C:38]2[O:37][CH2:36][CH2:35][CH2:34][C:33]=2[CH:32]=1)[C:8]([O:10][CH3:11])=[O:9])([CH3:16])([CH3:15])[CH3:14]

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 70819299Methyl 2-(2-bromo-5-phenylthiophen-3-yl)-2-(tert-butoxy)acetate

Product 1

HCID 70855249methyl 2-(tert-butoxy)-2-[2-(3,4-dihydro-2H-1-benzopyran-6-yl)-5-phenylthiophen-3-yl]acetateYield 70%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

A solution of methyl 2-(2-bromo-5-phenylthiophen-3-yl)-2-(tert-butoxy)acetate (11i) (77 mg, 0.20 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (94 mg, 0.36 mmol) and sodium carbonate (85 mg, 0.80 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 a 95° C. for 4 h. 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 85/15) to provide the desired product (11j) (60 mg, 0.14 mmol, 68%).

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 85/15)

Sources & evidence

ORD record
ord-1c16a4ca101442f995469fb7b5201df4
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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