Imidazole → (R)-N-[5-[2-Iodo-1-[((1,1-dimethylethyl)dimethylsilyl)oxy]ethyl]-2-(phenylmethoxy)phenyl]methanesulfonamide

HRID 964623Notes

Reaction equation

HRID 964623 reaction equation
CN(C=O)C.[I:6][CH2:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:11]=1)[OH:9].N1C=CN=C1.[Si:34](Cl)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]>CN(C)C1C=CN=CC=1.CCOC(C)=O.CCCCCCC>[I:6][CH2:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:11]=1)[O:9][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 53853223(R)-2-Iodo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanol

Product 1

HCID 67701180(R)-N-[5-[2-Iodo-1-[((1,1-dimethylethyl)dimethylsilyl)oxy]ethyl]-2-(phenylmethoxy)phenyl]methanesulfonamideYield 100.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

To a stirred DMF (65 mL) solution containing (R)-2-iodo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanol (12.7 g, 28 mmol), imidazole (5.25 g, 77 mmol), and 4-dimethylaminopyridine (0.30 g, 2.46 mmol) was added t-butyldimethylsilyl chloride (5.0 mL, 29.8 mmol). After 15 hours, the completed reaction was diluted with EtOAc (200 mL) and heptane (70 mL). The organic phase was washed 1×100 mL H2O, 2×100 mL aq. sat. CuSO4, 1×100 mL H2O, 1×100 mL sat'd brine, and dried over Na2SO4. The filtrate was concentrated in vacuo to give 15.81 g of a tan solid which was dissolved in ~125 mL CH2Cl2 and diluted with 650 mL heptane. The mixture was concentrated in vacuo at 40° C. to 42° C. until solids were seen (~105 mL distillate were collected), cooled to ~15° C. and filtered. The collected solids were washed with heptane and dried in vacuo at 45° C. to give 11.1 g (70%) of the title compound.

Workup

  1. customthe completed reaction
  2. washThe organic phase was washed 1×100 mL H2O, 2×100 mL aq. sat. CuSO4, 1×100 mL H2O, 1×100 mL
  3. dry with materialdried over Na2SO4
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-53c100f90aae4578851b6e8dc4d7ad60
Source dataset
uspto-grants-1998_06
Patent number
US05770615

Reaction notes

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