Triphenylphosphine → HCID 57937606, compound

HRID 1435114Notes

Reaction equation

HRID 1435114 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([N:7]2[C:11]3[CH:12]=[CH:13][C:14](OC(F)(F)F)=[CH:15][C:10]=3[N:9]=[CH:8]2)[S:4][C:3]=1[C:21]([O:23][CH3:24])=[O:22].[Cl:25][C:26]1[C:31]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])=[CH:30][CH:29]=[CH:28][C:27]=1[C@@H:40](O)[CH3:41].[C:43]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:48]=CC=C[CH:44]=1.CC(O[C:67](/[N:69]=[N:70]/C(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl>[Cl:25][C:26]1[C:31]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])=[CH:30][CH:29]=[CH:28][C:27]=1[C@H:40]([O:1][C:2]1[CH:6]=[C:5]([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:43]4[CH:48]=[N:70][N:69]([CH3:67])[CH:44]=4)=[CH:15][C:10]=3[N:9]=[CH:8]2)[S:4][C:3]=1[C:21]([O:23][CH3:24])=[O:22])[CH3:41]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 57937457HCID 57937457, compoundHCID 57937626HCID 57937626, compound2×

Product 1

HCID 57937606HCID 57937606, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a slurry of methyl 3-hydroxy-5-{5-[(trifluoromethyl)oxy]-1H-benzimidazol-1-yl}-2-thiophenecarboxylate (0.71 g, 2.0 mmol) and (1S)-1-(2-chloro-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}phenyl)ethanol (Intermediate 17, 0.63 g, 2.2 mmol) so DCM (20 mL) was added triphenylphosphine (1.1 g, 4.0 mmol) and di-tert-butylazodicarboxylate (0.92 g, 4.0 mmol). The clear, yellow solution was stirred for 1 h, then silica gel (5 g) was added. The volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 50% EtOAc:DCM) to give 1.1 g (1.8 mmol) of the methyl 3-{[(1R)-1-(2-chloro-3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}phenyl)ethyl]oxy}-5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-2-thiophenecarboxylate which was dissolved in THF (15 mL). 1 N tetrabutylammonium fluoride in THF (1.8 mL, 1.8 mmol) was added. After 10 min, silica (3 g) was added, the volatiles were evaporated under reduced pressure and the residue was purified by flash column chromatography (0 to 70% EtOAc:DCM) to afford 0.36 g (47%) of the title compound as a solid. 1H NMR (400 MHz, CD3OD): δ 8.48 (s, 1H), 7.63 (s, 1H), 7.40 (d, J=8.97 Hz, 1H), 7.30 (d, J=8.79 Hz, 1H), 7.13 (m, 2H), 7.0 (s, 1H), 6.8 (d, J=7.51 Hz, 1H), 5.95 (q, J=6.17 Hz, 1H), 3.88 (s, 3H), 1.68(d, J=6.23 Hz, 3H).

Workup

  1. additionsilica gel (5 g) was added
  2. customThe volatiles were evaporated under reduced pressure
  3. customthe residue was purified by flash column chromatography (0 to 50% EtOAc:DCM)

Sources & evidence

ORD record
ord-4805ee9236e640b8a45a2f9c7a6159f3
Source dataset
uspto-grants-2009_11
Patent number
US07615643B2

Reaction notes

Loading…