1,3-Bis(diphenylphosphino)propane → Methyl (R)-3-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-5-carboxylate

HRID 1253638Notes

Reaction equation

HRID 1253638 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][C@H:8]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CO.CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:14]([O:13][C:12]([NH:11][C@H:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([C:12]([O:13][CH3:14])=[O:18])[CH:10]=2)[CH2:6][CH2:7]1)=[O:18])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 2

HCID 812191,3-Bis(diphenylphosphino)propaneHCID 59505686(R)-(6-Bromo-indan-1-yl)-carbamic acid tert-butyl ester

Product 1

HCID 59505324Methyl (R)-3-((tert-butoxycarbonyl)amino)-2,3-dihydro-1H-indene-5-carboxylateYield 76%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

A solution of (R)-tert-butyl 6-bromo-2,3-dihydro-1H-inden-1-ylcarbamate (15.0 g, 48.07 mmol, 1.0 eq.) in a mixture of MeOH (200 ml) and DMSO (30 ml) was degassed with argon for 30 min followed by addition of palladium acetate (0.53 g, 2.40 mmol, 0.05 eq.), 1,3-bis(diphenylphosphino)propane (0.99 g, 2.40 mmol, 0.05 eq.) and TEA (20 ml, 144.21 mmol, 3.0 eq.). The reaction mixture was then sealed in an autoclave using CO pressure (80 psi) and heated at 75° C. for 16 h. The mixture was evaporated to dryness, diluted with water (150 ml) and extracted with ethyl acetate (2×300 ml). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na2SO4 and evaporated to give the crude product which was purified by column chromatography (silica gel; 5% ethyl acetate/hexanes) to yield the desired product as a white solid. Yield: 76% (10.6 g, 36.43 mmol).

Workup

  1. customwas degassed with argon for 30 min
  2. customThe reaction mixture was then sealed in an autoclave
  3. customThe mixture was evaporated to dryness
  4. additiondiluted with water (150 ml)
  5. extractionextracted with ethyl acetate (2×300 ml)
  6. washThe combined organic layers were washed with brine (100 ml)
  7. dry with materialdried over anhydrous Na2SO4
  8. customevaporated
  9. customto give the crude product which
  10. customwas purified by column chromatography (silica gel; 5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9de0ddcf505e49e981e40749a02d676e
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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