Dimethylformamide → methyl 1-(benzyloxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate

HRID 473095Notes

Reaction equation

HRID 473095 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:6][CH2:5]2.[C:22](=[O:25])([O-])[O-:23].[Na+].[Na+].[CH3:28]N(C=O)C>CO.CCOC(C)=O.[Cl-].[Na+].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]>[CH2:14]([O:13][C:12]([NH:11][CH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:22]([O:23][CH3:28])=[O:25])=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 67088086benzyl N-(5-bromo-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 67088132methyl 1-(benzyloxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

A 500 mL steel autoclave was charged with benzyl 5-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (7.50 g, 21.7 mmol), PdCl2(dppf) (890 mg, 1.1 mmol), and sodium carbonate (4.69 g, 44.3 mmol) in degassed DMF (50 mL) and methanol (50 mL). The autoclave was placed under carbon monoxide (12 bar) and stirred at 100° C. for 3 days. The reaction was cooled to rt, diluted with EtOAc (200 mL) and brine (200 mL), and filtered over Kiezelguhr gel. The organics were isolated and washed with brine (2×200 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford aa brown oil. This material was purified by flash column chromatography (300 g silica, EtOac/heptane, from 0% to 50% of EtOAc) to the title compound as a white solid (3.87 g, 52.2%). MS (ESI): m/z [M+H]+ 326.0

Workup

  1. temperatureThe reaction was cooled to rt
  2. filtrationfiltered over Kiezelguhr gel
  3. customThe organics were isolated
  4. washwashed with brine (2×200 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford aa brown oil
  9. customThis material was purified by flash column chromatography (300 g silica, EtOac/heptane, from 0% to 50% of EtOAc) to the title compound as a white solid (3.87 g, 52.2%)

Sources & evidence

ORD record
ord-5a0a84be4ab44e029cfd65347cdb5b45
Source dataset
uspto-grants-2014_01
Patent number
US08633237B2

Reaction notes

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