Diisopropylamine → HCID 66937209, compound

HRID 408702Notes

Reaction equation

HRID 408702 reaction equation
C(NC(C)C)(C)C.[Cl:8][C:9]1[C:10]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:11][C:12]2[N:16]=[CH:15][N:14]([CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[C:13]=2[CH:23]=1.[Cl:31]N1C(=O)CCC1=O.[NH4+].[Cl-]>C1COCC1>[Cl:31][C:15]1[N:14]([CH2:17][O:18][CH2:19][CH2:20][O:21][CH3:22])[C:13]2[CH:23]=[C:9]([Cl:8])[C:10]([O:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:11][C:12]=2[N:16]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 31398ChlorosuccinimideHCID 66937357HCID 66937357, compound

Product 1

HCID 66937209HCID 66937209, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (260 L, 1.85 mmol) in dry THF (2 mL) cooled in −78° C. bath was added n-buthyllithium in hexanes (1.16 mL of a 1.6 M solution). After 45 min, the contents of the flask were added via syringe to a −78° C. solution of 6-chloro-1-(2-methoxy-ethoxymethyl)-5-phenoxy-1H-benzoimidazole (0.560 g, 1.68 mmol) in dry THF (2 mL). After 60 min, N-chlorosuccinimide (0.247 g, 1.85 mmol) in THF (3 mL) was added via syringe to the dark solution at which time the color changed to light brown. The reaction mixture was allowed to warm to ambient temperature then was added to saturated aq. NH4Cl and extracted with EtOAc. The combined organic layers were washed with 0.5 M citric acid, 5% aq. NaHCO3, brine, dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) to yield the titled compound as a mixture of regioisomers (0.251 g, 41%; orange oil). MS (ESI/CI): mass calcd. for C17H16Cl2N2O3, 366; m/z found, 367 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.80 (s, 1H), 7.62 (s, 1H), 7.37 (s, 1H), 7.36-7.29 (m, 4H), 7.18 (s, 1H), 7.14-7.04 (m, 2H), 6.98-6.90 (m, 4H), 5.63 (s, 2H), 5.54 (s, 2H), 3.72-3.63 (m, 2H), 3.63-3.57 (m, 2H), 3.57-3.50 (m, 2H), 3.49-3.42 (m, 2H), 3.38 (s, 3H), 3.28 (s, 3H).

Workup

  1. waitAfter 60 min
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with 0.5 M citric acid, 5% aq. NaHCO3, brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified (FCC)

Sources & evidence

ORD record
ord-4b5bbdc52fed49cab88227886e801001
Source dataset
uspto-grants-2014_06
Patent number
US08759345B2

Reaction notes

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