Tetrahydrofuran → HCID 58354968, compound

HRID 1807596Notes

Reaction equation

HRID 1807596 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=O.[CH3:12][C:13]([S@:16]([NH2:18])=[O:17])([CH3:15])[CH3:14].C1COCC1.[BH4-].[Na+]>C1(C)C=CC=CC=1.[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C@H:6]2[NH:18][S@@:16]([C:13]([CH3:15])([CH3:14])[CH3:12])=[O:17]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 987131-Indanone, 4-bromo-HCID 4311764Sodium borohydrideHCID 10964479tert-Butylsulfinamide, (R)-(+)-

Product 1

HCID 58354968HCID 58354968, compound

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirring solution of 4-bromo-2,3-dihydro-1H-inden-1-one (5.0 g, 23.6 mmol) and (R)-2-methylpropane-2-sulfinamide (3.15 g, 26.0 mmol) in toluene (40 mL) was added titanium tetraethoxide (8.1 g, 35.5 mmol) and the reaction mixture was heated at 60° C. for 18 h under N2. To this mixture was added THF (40 mL) and the resulting solution was cooled to −78° C. Sodium borohydride (3.5 g, 94.7 mmol) was added in one portion. The reaction mixture was stirred at −78° C. for 15 min, and then warmed to room temperature and stirred at this temperature for 2 h. The reaction mixture was cooled to 0° C. before quenching with brine and sodium potassium-tartrate. EA was added and the mixture was stirred at room temperature overnight during which time Ti salts precipitated. The organic layers were decanted, and washed successively with saturated NH4Cl, water, and brine. The organic layers were dried over MgSO4, filtered through a pad of MgSO4, and concentrated to produce (R)-N-((R)-4-bromo-2,3-dihydro-1H-inden-1-yl)-2-methylpropane-2-sulfinamide INT-34 as a solid (3.14 g, 42%) which was used in the next step without purification. LCMS-ESI (m/z) calculated C13H18BrNOS: 317.3; found 318.0 [M+H]+, tR=3.59 min. 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J=7.5, 1H), 7.34 (d, J=7.9, 1H), 7.05 (t, J=7.7, 1H), 4.96-4.77 (m, 1H), 3.39 (d, J=6.8, 1H), 3.06-2.86 (m, 1H), 2.82-2.60 (m, 1H), 2.50-2.29 (m, 1H), 2.05-1.81 (m, 1H), 1.16 (s, 9H).

Workup

  1. temperaturethe resulting solution was cooled to −78° C
  2. temperaturewarmed to room temperature
  3. stirringstirred at this temperature for 2 h
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. custombefore quenching with brine and sodium potassium-tartrate
  6. additionEA was added
  7. stirringthe mixture was stirred at room temperature overnight during which time Ti salts
  8. customprecipitated
  9. customThe organic layers were decanted
  10. washwashed successively with saturated NH4Cl, water, and brine
  11. dry with materialThe organic layers were dried over MgSO4
  12. filtrationfiltered through a pad of MgSO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-82c94c03de514d26a42e17511ee7c093
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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