Ammonium Chloride → HCID 66937304, compound

HRID 408710Notes

Reaction equation

HRID 408710 reaction equation
[Cl:1][C:2]1[C:3]([S:17][C:18]2[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=2)=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][O:11][CH2:12][CH2:13][O:14][CH3:15])[C:6]=2[CH:16]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:33]N1C(=O)CCC1=O.[NH4+].[Cl-]>C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C.C1COCC1>[Cl:33][C:8]1[N:7]([CH2:10][O:11][CH2:12][CH2:13][O:14][CH3:15])[C:6]2[CH:16]=[C:2]([Cl:1])[C:3]([S:17][C:18]3[CH:19]=[C:20]([CH3:24])[CH:21]=[CH:22][CH:23]=3)=[CH:4][C:5]=2[N:9]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 31398ChlorosuccinimideHCID 2724682Lithium diisopropylamideHCID 66937061HCID 66937061, compound

Product 1

HCID 66937304HCID 66937304, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
23 °C

Procedure

A solution of 6-chloro-1-(2-methoxy-ethoxymethyl)-5-m-tolylsulfanyl-1H-benzoimidazole (1.89 g, 5.21 mmol) and THF (13 mL) was cooled to −78° C. in an acetone/dry ice bath. Buthyllithium (2.2M solution in hexanes, 2.60 mL, 5.73 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 1 h. (Lithium diisopropylamide as a 2.0M solution in THF/heptane/ethylbenzene can also be used as a base.) A solution of N-chlorosuccinimide (765 mg, 5.73 mmol) and THF (11.5 mL) was added. The reaction mixture was warmed to 23° C. and stirred for 2 h. Saturated aqueous NH4Cl (20 mL) was added and the crude product was extracted into CH2Cl2 (3×75 mL). The organic layers were dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (0-100% EtOAc/hexanes) to provide the titled compound (1.46 g, 71%) as a 1:1 mixture of regioisomers. MS (ESI/CI): mass calcd. for C18H18Cl2N2O2S, 396.0; m/z found, 397.0 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.74 (s, 1H), 7.57 (s, 1H), 7.40 (s, 1H), 7.29 (s, 1H), 7.23-7.18 (m, 3H), 7.18-7.14 (m, 2H), 7.12-7.07 (m, 3H), 5.58 (s, 2H), 5.48 (s, 2H), 3.64-3.60 (m, 2H), 3.54-3.48 (m, 4H), 3.43-3.40 (m, 2H), 3.34 (s, 3H), 3.29 (s, 3H), 2.30 (s, 6H).

Workup

  1. extractionthe crude product was extracted into CH2Cl2 (3×75 mL)
  2. customThe organic layers were dried
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified (FCC) (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-446fbf4f30c4428dab4ce2c32e7e0535
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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