Thioanisole → 2-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-7-nitro-1H-indol-5-yl pivalate

HRID 1994841Notes

Reaction equation

HRID 1994841 reaction equation
C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[C:36]([O:42][C:43]1[CH:44]=[C:45]2[C:49](=[C:50]([N+:52]([O-:54])=[O:53])[CH:51]=1)[NH:48][C:47]([C:55]([NH:57][CH2:58][CH:59]([S:65]CC1C=CC=CC=1)[CH:60]([O:63][CH3:64])[O:61][CH3:62])=O)=[CH:46]2)(=[O:41])[C:37]([CH3:40])([CH3:39])[CH3:38].C1(SC)C=CC=CC=1.C(=O)([O-])O.[Na+]>ClCCl>[C:36]([O:42][C:43]1[CH:44]=[C:45]2[C:49](=[C:50]([N+:52]([O-:54])=[O:53])[CH:51]=1)[NH:48][C:47]([C:55]1[S:65][CH:59]([CH:60]([O:61][CH3:62])[O:63][CH3:64])[CH2:58][N:57]=1)=[CH:46]2)(=[O:41])[C:37]([CH3:39])([CH3:38])[CH3:40]

Participants

7

Reactant 5

HCID 7520ThioanisoleHCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 516892Sodium BicarbonateHCID 575032112-(([2-(benzylthio)-3,3-dimethoxypropyl]amino}carbonyl)-7-nitro-1H-indol-5-yl pivalate

Product 1

HCID 575032102-[5-(dimethoxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]-7-nitro-1H-indol-5-yl pivalateYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of triphenylphosphine oxide (14.8 g) in dichloromethane (50 mL) was added dropwise trifluoromethanesulfonic anhydride (3.0 mL) under ice-cooling, and the mixture was stirred for 30 min. A solution of 2-({[2-(benzylthio)-3,3-dimethoxypropyl]amino}carbonyl)-7-nitro-1H-indol-5-yl pivalate (9.38 g) and thioanisole (10.4 mL) in dichloromethane (100 mL) was added dropwise to this solution at −78° C., and the reaction mixture was stirred at −78° C. for 1 hr, and then at 0° C. for 1 hr. Saturated aqueous sodium hydrogencarbonate was added, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried (MgSO4), and concentrated. The residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=1:0-4:6) to give the title compound (4.32 g, yield 58%) as a pale-yellow amorphous powder. MS: 422 (MH+).

Workup

  1. temperaturecooling
  2. stirringthe reaction mixture was stirred at −78° C. for 1 hr
  3. waitat 0° C. for 1 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe combined organic layer was washed with water and saturated brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=1:0-4:6)

Sources & evidence

ORD record
ord-4fee7f5ac6d34fb190d38efce427fa9f
Source dataset
uspto-grants-2010_01
Patent number
US07652133B2

Reaction notes

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