Sodium Carbonate → methyl 3-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-5-(trifluoromethyl)benzoate

HRID 473098Notes

Reaction equation

HRID 473098 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH:8]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][CH2:6]2.CC1(C)COB([C:30]2[CH:31]=[C:32]([CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:39]=2)[C:33]([O:35][CH3:36])=[O:34])OC1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(OCC)(=O)C.C1C(=O)[N-]C(=O)C1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[Pd+]>[CH2:15]([O:14][C:13]([NH:12][CH:8]1[C:9]2[C:5](=[CH:4][C:3]([CH2:2][C:30]3[CH:31]=[C:32]([CH:37]=[C:38]([C:40]([F:41])([F:43])[F:42])[CH:39]=3)[C:33]([O:35][CH3:36])=[O:34])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66734229Methyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(trifluoromethyl)benzoateHCID 70220201benzyl 5-(chloromethyl)-2,3-dihydro-1H-inden-1-ylcarbamate

Product 1

HCID 68155834methyl 3-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-5-(trifluoromethyl)benzoateYield 87%

Reagents, catalysts & solvents 4

HCID 11434313trans-Bromo(N-succinimidyl)bis(triphenylphosphine)palladium(II)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of benzyl 5-(chloromethyl)-2,3-dihydro-1H-inden-1-ylcarbamate (2.10 g, 6.7 mmol), methyl 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-5-(trifluoromethyl)benzoate (2.21 g, 7.0 mmol), trans-Bromo(N-succinimidyl)bis(triphenylphosphine)palladium(II) (269 mg, 0.3 mmol), and sodium carbonate (3.52 g, 33.2 mmol) in degassed THF (40 mL) and water (20 mL) was stirred at 80° C. After 3 h the reaction was cooled to rt and diluted with ethyl acetate (200 mL) and washed with brine (2×200 mL). The aqueous phases were extracted once more with ethyl acetate (1×100 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford a grey solid. The material was purified by silica flash column chromatography (100 g silica, EtOAc/heptane, from 0% to 25% of EtOAc) to afford the title compound as a white solid (2.8 g, 87%). MS (ESI): m/z [M+NH4]+ 501.2.

Workup

  1. temperatureAfter 3 h the reaction was cooled to rt
  2. washwashed with brine (2×200 mL)
  3. extractionThe aqueous phases were extracted once more with ethyl acetate (1×100 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford a grey solid
  8. customThe material was purified by silica flash column chromatography (100 g silica, EtOAc/heptane, from 0% to 25% of EtOAc)

Sources & evidence

ORD record
ord-b5d1109a4651449090bedd1c801a7fb4
Source dataset
uspto-grants-2014_01
Patent number
US08633237B2

Reaction notes

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