N,N,N',N'-Tetramethylazodicarboxamide → Ethyl[4-(2-{5-[bis(4-fluorophenyl)methyl]-2-oxopyridin-1(2h)-yl}ethoxy)-2-methyl-1h-benzimidazol-1-yl]acetate

HRID 2389327Notes

Reaction equation

HRID 2389327 reaction equation
[OH:1][C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=2)[C:26]2[CH:27]=[CH:28][C:29](=[O:35])[N:30]([CH2:32][CH2:33]O)[CH:31]=2)=[CH:21][CH:20]=1.N(C(N(C)C)=O)=NC(N(C)C)=O.C(P(CCCC)CCCC)CCC>C1COCC1.C1(C)C=CC=CC=1>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][N:7]1[C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([O:1][CH2:33][CH2:32][N:30]3[CH:31]=[C:26]([CH:25]([C:22]4[CH:21]=[CH:20][C:19]([F:18])=[CH:24][CH:23]=4)[C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[CH:27]=[CH:28][C:29]3=[O:35])[C:10]=2[N:9]=[C:8]1[CH3:11])[CH3:17]

Participants

7

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 685335945-[Bis(4-fluorophenyl)methyl]-1-(2-hydroxyethyl)pyridin-2(1h)-oneHCID 86637909ethyl (4-hydroxy-2-methyl-1H-benzimidazol-1-yl)acetate

Product 1

HCID 131729955Ethyl[4-(2-{5-[bis(4-fluorophenyl)methyl]-2-oxopyridin-1(2h)-yl}ethoxy)-2-methyl-1h-benzimidazol-1-yl]acetateYield 94.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethyl (4-hydroxy-2-methyl-1H-benzimidazol-1-yl)acetate (476 mg), 5-[bis(4-fluorophenyl)methyl]-1-(2-hydroxyethyl)pyridin-2(1H)-one (694 mg), 1,1′-azobis(N,N-dimethylformamide) (385 mg) and toluene (9.5 mL) was added tributylphosphine (452 mg) at ambient temperature. The mixture was stirred at ambient temperature for 20 hours. The reaction mixture was diluted with a mixture of EtoAc (50 mL) and THF (20 mL), and washed with water (30 mL) and brine (30 mL). The organic layer was dried over anhydrous MgSO4, filtered and evaporated in vacuo to give crude oil. The crude oil was crystallized from solvent(EtOAc and n-hexane) to give ethyl[4-(2-{5-[bis(4-fluorophenyl)methyl]-2-oxopyridin-1(2H)-yl}ethoxy)-2-methyl-1H-benzimidazol-1-yl]acetate (1.07 g) as a white solid.

Workup

  1. washwashed with water (30 mL) and brine (30 mL)
  2. dry with materialThe organic layer was dried over anhydrous MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customto give crude oil
  6. customThe crude oil was crystallized from solvent(EtOAc and n-hexane)

Sources & evidence

ORD record
ord-1929e57b2c1b460eb7c3ef091f5d99cd
Source dataset
uspto-grants-2012_09
Patent number
US08273745B2

Reaction notes

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