Triphenylphosphine → 1-[(1R)-3-chloro-1-(3-chloro-5-fluorophenyl)propyl]-3-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

HRID 1819670Notes

Reaction equation

HRID 1819670 reaction equation
[CH:1]([N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][S:5]1(=[O:14])=[O:13])([CH3:3])[CH3:2].[Cl:15][CH2:16][CH2:17][C@@H:18]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([Cl:27])[CH:21]=1)O.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>O1CCCC1>[Cl:15][CH2:16][CH2:17][C@@H:18]([N:6]1[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:4]([CH:1]([CH3:3])[CH3:2])[S:5]1(=[O:13])=[O:14])[C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([Cl:27])[CH:21]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 596406791-(Propan-2-yl)-1,3-dihydro-2lambda6,1,3-benzothiadiazole-2,2-dioneHCID 68523631(1S)-3-chloro-1-(3-chloro-5-fluorophenyl)propan-1-ol

Product 1

HCID 690592361-[(1R)-3-chloro-1-(3-chloro-5-fluorophenyl)propyl]-3-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxideYield 82.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To mixture of 1-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (1.28 g, 6.00 mmol), (1S)-3-chloro-1-(3-chloro-5-fluorophenyl)propan-1-ol (1.34 g, 6.00 mmol) and triphenylphosphine (1.73 g, 6.60 mmol, 1.1 equiv.) in tetrahydrofuran (20 mL) under nitrogen was added slowly diisopropyl azodicarboxylate (1.28 mL, 6.60 mmol, 1.1 equiv.) via a syringe at 0° C. The resulting solution was stirred at room temperature overnight. Solvent was removed under reduced pressure and the viscous brown liquid residue was purified using Isco CombiFlash Companion column chromatography (silica gel, 0-15% ethyl acetate/hexane) to give 2.06 g (82%) of 1-[(1R)-3-chloro-1-(3-chloro-5-fluorophenyl)propyl]-3-isopropyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide as a white solid.

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe viscous brown liquid residue was purified

Sources & evidence

ORD record
ord-9db34d61306b4800b8c92367317d6318
Source dataset
uspto-grants-2009_10
Patent number
US07601744B2

Reaction notes

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