Methanol → HCID 90043134, compound

HRID 1050268Notes

Reaction equation

HRID 1050268 reaction equation
[C:1]1([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@@H:25]4[CH2:30][C@H:29]([O:31][Si:32]([CH2:37][CH3:38])([CH2:35][CH3:36])[CH2:33][CH3:34])[C@@H:28]([CH2:39][O:40][Si](CC)(CC)CC)[O:27][CH2:26]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[CH:9][C:8]=2[Cl:48])=[CH:3][CH:2]=1.CO.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]1([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:6]=[CH:5][C:4]([C:7]2[N:12]=[C:11]3[N:13]=[C:14]([O:24][C@H:25]4[CH2:26][O:27][C@H:28]([CH2:39][OH:40])[C@@H:29]([O:31][Si:32]([CH2:37][CH3:38])([CH2:33][CH3:34])[CH2:35][CH3:36])[CH2:30]4)[N:15]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:10]3=[CH:9][C:8]=2[Cl:48])=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 22033616Pyridinium.p-toluenesulfonateHCID 131736059HCID 131736059, compound

Product 1

HCID 90043134HCID 90043134, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of 5-([1,1′-biphenyl]-4-yl)-6-chloro-2-(((3R,5S,6R)-5-((triethylsilyl)oxy)-6-(((triethylsilyl)oxy)-methyl)tetrahydro-2H-pyran-3-yl)oxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine (99 mg, 0.122 mmol) under nitrogen in DCM (2.0 mL) and methanol (2.0 mL) at −20° C. was added pyridinium-paratoluenesulfonic acid (6 mg, 0.024 mmol). After stirring for 2.5 hours at −20° C., the mixture was poured into saturated aqueous sodium bicarbonate (40 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resultant oil was chromatographed using a Biotage™ 20 g (2×10 g in series) silica gel cartridge eluted with 0-20% EtOAc in 1:1 Hexane/DCM over 15 column volumes, then 20-100% EtOAc over 10 column volumes. The desired SEM regiosiomeric products were combined and concentrated under reduced pressure to provide the title compound as a clear oil. LC-MS: calculated for C36H50ClN3O5Si2 695.30, observed m/e: 696.23 (M+H)+ (Rt 3.26/4 min, minor isomer), 696.23 (M+H)+ (Rt 3.39/4 min, major isomer).

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. washThe combined organic layers were washed with brine (40 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resultant oil was chromatographed
  6. washeluted with 0-20% EtOAc in 1:1 Hexane/DCM over 15 column volumes
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ae394e293be741e7b22f8ef49a1b8c18
Source dataset
uspto-grants-2016_07
Patent number
US09382243B2

Reaction notes

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