Triphenylphosphine → Methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{1-[4-fluoro-2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxylate

HRID 2391712Notes

Reaction equation

HRID 2391712 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[C:21]([OH:28])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH:36](O)[CH3:37])=[C:32]([C:39]([F:42])([F:41])[F:40])[CH:31]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[Si:1]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([O:26][CH3:27])=[O:25])=[C:21]([O:28][CH:36]([C:33]4[CH:34]=[CH:35][C:30]([F:29])=[CH:31][C:32]=4[C:39]([F:42])([F:40])[F:41])[CH3:37])[CH:20]=3)[C:12]=2[CH:11]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 68766707methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-hydroxythiophene-2-carboxylateHCID 68766857HCID 68766857, compound

Product 1

HCID 68764933Methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{1-[4-fluoro-2-(trifluoromethyl)phenyl]ethoxy}thiophene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere, 2.1 g of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-hydroxythiophene-2-carboxylate are dissolved in 60 ml anhydrous dichloromethane. Consecutively, 1.56 g of 1-[4-fluoro-2-(trifluoromethyl)phenyl]ethanol, 3.3 g triphenylphosphine (polymer bound, ˜3 mmol/g) and 2.3 g of di-tert-butyl azodicarboxylate are added to the solution. The reaction mixture is stirred at room temperature for 15 h and then filtered. The filter cake is washed with 50 ml of a dichloromethane/methanol mixture (95:5). The filtrate is concentrated to dryness under reduced pressure. The crude is purified by flash chromatography [Silica gel, eluent: ethyl acetate/cyclohexane, elution gradient of 5/95 (v/v) to 70/30 (v/v) to yield the title product.

Workup

  1. filtrationfiltered
  2. washThe filter cake is washed with 50 ml of a dichloromethane/methanol mixture (95:5)
  3. concentrationThe filtrate is concentrated to dryness under reduced pressure
  4. customThe crude is purified by flash chromatography [Silica gel, eluent
  5. washethyl acetate/cyclohexane, elution gradient of 5/95 (v/v) to 70/30 (v/v)

Sources & evidence

ORD record
ord-adbfdcd9be9d42f09ac80453fee83fed
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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