Methanol → Methyl 1-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylate

HRID 43029Notes

Reaction equation

HRID 43029 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[CH2:6][CH2:5]2.[C:18](=[O:21])([O-])[O-:19].[Na+].[Na+].[CH3:24]O>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:16][CH:15]([S:12]([NH:11][CH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:18]([O:19][CH3:24])=[O:21])=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)(=[O:14])=[O:13])[CH3:17]

Participants

5

Reactant 3

HCID 887MethanolHCID 10340Sodium CarbonateHCID 66733842N-(5-bromo-2,3-dihydro-1H-inden-1-yl)propane-2-sulfonamide

Product 1

HCID 67088221Methyl 1-(1-methylethylsulfonamido)-2,3-dihydro-1H-indene-5-carboxylateYield 22%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
100 °C

Procedure

A 150 mL steel autoclave was charged with N-(5-bromo-2,3-dihydro-1H-inden-1-yl)propane-2-sulfonamide (4.85 g, 15.24 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium(II)dichloride (0.622 g, 0.762 mmol), and sodium carbonate (3.23 g, 30.5 mmol) in degassed methanol. The autoclave was placed under carbon monoxide atmosphere (12 bar) and stirred at 100° C. for 24 hr. After this time, catalyst and Na2CO3 were filtered off and replaced with a new batch and the reaction was stirred for 24 hr at 100° C. and 12 bar CO. The mixture was filtered and partitioned between EtOAc and brine, organic layer separated, washed with brine. To the organic layer was added silica and Na2SO4 added and stirred for 20 min. The whole was filtered and solvent evaporated in vacuo to give a brown oil. Purification by flash chromatography (0-50% EtOAc in heptane) afforded the title compound as a yellow/brown oil (1 g, 22%). 1H NMR (400 MHz, CDCl3) δ 1.46 (d, 6H) 1.95 (m, 1H) 2.65 (m, 1H) 2.85 (m, 1H) 3.00 (m, 1H) 3.25 (m, 1H) 3.91 (s, 3H) 4.25 (d, 1H) 5.00 (q, 1H) 7.50 (d, 1H) 7.90 (m, 2H).

Workup

  1. filtrationAfter this time, catalyst and Na2CO3 were filtered off
  2. stirringthe reaction was stirred for 24 hr at 100° C.
  3. filtrationThe mixture was filtered
  4. custompartitioned between EtOAc and brine, organic layer
  5. customseparated
  6. washwashed with brine
  7. additionTo the organic layer was added silica and Na2SO4
  8. additionadded
  9. stirringstirred for 20 min
  10. filtrationThe whole was filtered
  11. customsolvent evaporated in vacuo
  12. customto give a brown oil
  13. customPurification by flash chromatography (0-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-1753a3c405a74d1ba4f826d572b980bb
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

Loading…