Dichloromethane → HCID 57545940, compound

HRID 913951Notes

Reaction equation

HRID 913951 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:12][OH:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:7]=2)[CH:3]=1.CCN(CC)CC.C(Cl)Cl.[CH3:54][S:55](Cl)(=[O:57])=[O:56]>>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:12][O:13][S:55]([CH3:54])(=[O:57])=[O:56])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:41])[CH3:42])[N:7]=2)[CH:3]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 57545941HCID 57545941, compound

Product 1

HCID 57545940HCID 57545940, compoundYield 92.2%

Procedure

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-hydroxyethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (150 mg, 0.236 mmol) and Et3N (0.099 mL, 0.709 mmol) in DCM (3 mL, 46.6 mmol) at 0 C was added Methanesulfonyl chloride (0.037 mL, 0.473 mmol). The ice bath was removed and stirring continued for 1 h. The reaction was cooled to 0 , quenched by addition of saturated NaHCO3 and diluted with ether, the layers were separated and the ether layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by Biotage LC (30% EtOAc/Hex) to give 155 mg of title product as white foam (92% yield). LC/MS (HPLC method 3): tR=4.15 min, 712.3(MH)+.

Workup

  1. customThe ice bath was removed
  2. temperatureThe reaction was cooled to 0
  3. customquenched by addition of saturated NaHCO3
  4. additiondiluted with ether
  5. customthe layers were separated
  6. washthe ether layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by Biotage LC (30% EtOAc/Hex)

Sources & evidence

ORD record
ord-43ff86a94daf4414b25a5f90f77f9dbd
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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