Triphenylphosphine → (S)-7-bromo-3-methyl-1-tosyl-1,2,3,4-tetrahydroquinoxaline

HRID 1485666Notes

Reaction equation

HRID 1485666 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:19][C@@H:20]([CH3:23])[CH2:21]O)=[C:6]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]2[C:5]([NH:19][C@@H:20]([CH3:23])[CH2:21][N:8]2[S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 118079189(S)-N-(5-bromo-2-(1-hydroxypropan-2-ylamino)phenyl)-4-methylbenzenesulfonamide

Product 1

HCID 118079321(S)-7-bromo-3-methyl-1-tosyl-1,2,3,4-tetrahydroquinoxalineYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 3-L, three-necked, round bottomed flask fitted with a nitrogen inlet, overhead stirrer, and thermocouple was charged with (S)-N-(5-bromo-2-(1-hydroxypropan-2-ylamino)phenyl)-4-methylbenzenesulfonamide (77.0 g, 193 mmol), THF (1925 mL), and triphenylphosphine (60.7 g, 231 mmol). The solution was cooled to 0° C., and diisopropyl azodicarboxylate (DIAD) (41.2 mL, 212 mmol) was slowly added while maintaining the internal temperature below 7° C. The reaction mixture stirred at 0° C. for 1.5 h and was then warmed to room temperature. The mixture was concentrated and the residue was purified by column chromatography on silica gel (eluting with dichloromethane). The product-containing fraction were combined and concentrated under reduced pressure. The material was treated with a mixture of 4:1 hexanes-dichloromethane, and the slurry was stirred for 3 h and then filtered. The solids were rinsed with cold (ca. 0° C.) solution of 4:1 hexanes-dichloromethane (50 mL) and dried to afford (S)-7-bromo-3-methyl-1-tosyl-1,2,3,4-tetrahydroquinoxaline (61.8 g, 84%) as a white solid. MS (ESI, pos. ion) m/z 381 [M+1]+.

Workup

  1. temperaturewhile maintaining the internal temperature below 7° C
  2. temperaturewas then warmed to room temperature
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by column chromatography on silica gel (eluting with dichloromethane)
  5. concentrationconcentrated under reduced pressure
  6. additionThe material was treated with a mixture of 4:1 hexanes-dichloromethane
  7. stirringthe slurry was stirred for 3 h
  8. filtrationfiltered
  9. washThe solids were rinsed with cold (ca. 0° C.) solution of 4:1 hexanes-dichloromethane (50 mL)
  10. customdried

Sources & evidence

ORD record
ord-197abb9101df49c49f06922ce372469b
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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