Tributylphosphine → N-tosyl Tegoprazan

HRID 2239303Notes

Reaction equation

HRID 2239303 reaction equation
[OH:1][C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:6]=2[CH:5]=[C:4]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:3]=1.[F:27][C:28]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]2[C:29]=1[CH:30](O)[CH2:31][CH2:32][O:33]2.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1>[F:27][C:28]1[CH:37]=[C:36]([F:38])[CH:35]=[C:34]2[C:29]=1[C@@H:30]([O:1][C:2]1[C:10]3[N:9]=[C:8]([CH3:11])[N:7]([S:12]([C:15]4[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=4)(=[O:14])=[O:13])[C:6]=3[CH:5]=[C:4]([C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[CH:3]=1)[CH2:31][CH2:32][O:33]2

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 534275145,7-Difluorochroman-4-olHCID 672203154-Hydroxy-N,N,2-trimethyl-1-((4-methylphenyl)sulfonyl)-1H-benzimidazole-6-carboxamide

Product 1

HCID 68574320N-tosyl TegoprazanYield 75.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred mixture of 4-hydroxy-N,N,2-trimethyl-1-[(4-methylphenyl)sulfonyl]-1H-benzimidazole-6-carboxamide (21.2 g, 56.8 mmol, STEP 4), (+)-5,7-difluoro-3,4-dihydro-2H-chromen-4-ol (15.86 g, 85.1 mmol, STEP 8) and tributylphosphine (22.9 g, 113 mmol) in toluene (840 mL) was added 1,1′-(azodicarbonyl)dipiperidine (ADDP) (19.3 g, 76.5 mmol) at room temperature. After stirring at room temperature for 2 hours, the reaction mixture was filtered through a pad of Celite and washed with ethyl acetate (300 mL). The filtrate was concentrated in vacuum. The residue was purified by column chromatography on silica get (ethyl acetate:hexane gradient elution from 1:20 to 20:1) to afford crude solids (27.0 g). The solids were recrystallized from 2-propanol (130 mL) to give the title compound as a colorless crystal (23.2 g, 75%, >99% ee)

Workup

  1. filtrationthe reaction mixture was filtered through a pad of Celite
  2. washwashed with ethyl acetate (300 mL)
  3. concentrationThe filtrate was concentrated in vacuum
  4. customThe residue was purified by column chromatography on silica
  5. customget
  6. wash(ethyl acetate:hexane gradient elution from 1:20 to 20:1)
  7. customto afford crude solids (27.0 g)
  8. customThe solids were recrystallized from 2-propanol (130 mL)

Sources & evidence

ORD record
ord-f07b03fe30d44c3dbff6e51642814eed
Source dataset
uspto-grants-2010_05
Patent number
US07723321B2

Reaction notes

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