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

HRID 591013Notes

Reaction equation

HRID 591013 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].O.CC1(C)C(C)(C)OB([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[O:22][CH2:21][CH2:20][CH2:19]3)O1.Br[C:28]1[S:32][C:31]([CH3:33])=[N:30][C:29]=1[CH:34]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C:35]([O:37][CH3:38])=[O:36]>CN(C)C=O.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]>[C:40]([O:39][CH:34]([C:29]1[N:30]=[C:31]([CH3:33])[S:32][C:28]=1[C:16]1[CH:25]=[CH:24][C:23]2[O:22][CH2:21][CH2:20][CH2:19][C:18]=2[CH:17]=1)[C:35]([O:37][CH3:38])=[O:36])([CH3:43])([CH3:42])[CH3:41]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 438110342-(3,4-dihydro-2H-1-benzopyran-6-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 70819398Methyl 2-(5-bromo-2-methyl-1,3-thiazol-4-yl)-2-(tert-butoxy)acetate

Product 1

HCID 70855252methyl 2-(tert-butoxy)-2-[5-(3,4-dihydro-2H-1-benzopyran-6-yl)-2-methyl-1,3-thiazol-4-yl]acetateYield 61.9%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Under a nitrogen atmosphere, sodium carbonate (22 mg, 0.21 mmol), water (1 mL), palladium tetrakis(triphenylphosphine) (32 mg, 0.03 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (55 mg, 0.21 mmol) were added to a solution of methyl 2-(5-bromo-2-methyl-1,3-thiazol-4-yl)-2-(tert-butoxy)acetate (15d) (70 mg, 0.21 mmol) in N,N-dimethylformamide (4 mL). The mixture was heated at 110° C. for 1 hour. The mixture was then cooled at room temperature, concentrated and water (20 mL) was added. The aqueous layer was extracted with ethyl acetate (2×20 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 90/10) to afford the desired product as a white solid (48 mg, 0.13 mmol, 61%).

Workup

  1. temperatureThe mixture was then cooled at room temperature
  2. concentrationconcentrated
  3. additionwater (20 mL) was added
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×20 mL)
  5. washThe organic layer was washed with brine (20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 90/10)

Sources & evidence

ORD record
ord-577a95a2c76a49579f09018e62bae772
Source dataset
uspto-grants-2016_01
Patent number
US09238026B2

Reaction notes

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