Iodine → tert-Butyl 5-(tert-butyldiphenylsilanyloxy)-3-[4-iodo-5-(3-isobutylcyclobutyl)isoxazol-3-yl]valerate

HRID 1912053Notes

Reaction equation

HRID 1912053 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][CH:21]([C:30](=[N:41][O:42]C)[C:31]#[C:32][CH:33]1[CH2:36][CH:35]([CH2:37][CH:38]([CH3:40])[CH3:39])[CH2:34]1)[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:44]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[Si:1]([O:18][CH2:19][CH2:20][CH:21]([C:30]1[C:31]([I:44])=[C:32]([CH:33]2[CH2:36][CH:35]([CH2:37][CH:38]([CH3:39])[CH3:40])[CH2:34]2)[O:42][N:41]=1)[CH2:22][C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])([C:14]([CH3:15])([CH3:17])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 807IodineHCID 24477Sodium ThiosulfateHCID 86675035tert-Butyl 3-[2-(tert-butyldiphenylsilanyloxy)ethyl]-6-(3-isobutylcyclobutyl)-4-methoxyimino-5-hexynoate

Product 1

HCID 71127322tert-Butyl 5-(tert-butyldiphenylsilanyloxy)-3-[4-iodo-5-(3-isobutylcyclobutyl)isoxazol-3-yl]valerateYield 60.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 3-[2-(tert-butyldiphenylsilanyloxy)ethyl]-6-(3-isobutylcyclobutyl)-4-methoxyimino-5-hexynoate (53.6 g) and acetonitrile (320 mL) were mixed. To the mixture was added iodine (49.6 g) at ice temperature and the reaction mixture was stirred for 3 hr. After pouring the mixture into the solution of aqueous 20 w/v % sodium thiosulfate (380 mL) at ice temperature, the mixture was extracted with chloroform (1 L) and dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo. After an addition of silica gel (80 g) and ethyl acetate/hexane=1/20 (600 mL) to the residue, the mixture was stirred at RT for 1 hr. The silica gel was filtered off and the filtrate was concentrated in vacuo. The residue was purified twice by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/60→1/50→1/45) to give the title compound (38.2 g).

Workup

  1. extractionthe mixture was extracted with chloroform (1 L)
  2. dry with materialdried over magnesium sulfate
  3. filtrationThe magnesium sulfate was filtered off
  4. concentrationthe filtrate was concentrated in vacuo
  5. additionAfter an addition of silica gel (80 g) and ethyl acetate/hexane=1/20 (600 mL) to the residue
  6. stirringthe mixture was stirred at RT for 1 hr
  7. filtrationThe silica gel was filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customThe residue was purified twice by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/60→1/50→1/45)

Sources & evidence

ORD record
ord-3259f3e9001a4b9bb4ff255a6f2b283a
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

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