Hydrochloric Acid → (S)-2-{(R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetylamino-}4,4-dimethyl-pentanoic acid(2-fluoro-4-iodo-phenyl)-amide

HRID 1433776Notes

Reaction equation

HRID 1433776 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH2:37][O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[CH:31][CH:30]=1)[C:9](=[O:28])[NH:10][C@H:11]([C:17](=[O:27])[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])(C)(C)C.Cl.O1CCOCC1>C(#N)C>[F:26][C:20]1[CH:21]=[C:22]([I:25])[CH:23]=[CH:24][C:19]=1[NH:18][C:17](=[O:27])[C@@H:11]([NH:10][C:9](=[O:28])[C@H:8]([NH2:7])[C:29]1[CH:30]=[CH:31][C:32]([O:35][CH2:36][CH2:37][O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[CH:33][CH:34]=1)[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 68619010{(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}-carbamic acid tert-butyl ester

Product 1

HCID 69304181(S)-2-{(R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetylamino-}4,4-dimethyl-pentanoic acid(2-fluoro-4-iodo-phenyl)-amideYield 87.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (652 mg, 0.91 mmol) in acetonitrile (6 mL) was added 4 N hydrogen chloride in dioxane (1 mL, 4 mmol) and the mixture stirred at 40° C. for 30 minutes. The reaction mixture was concentrated in vacuo and the residue suspended in ice cold water. The aqueous suspension was neutralized to basic pH with saturated aqueous sodium carbonate solution then extracted with dichloromethane (three times). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo and the residue purified by chromatography over silica gel gradient eluted from 100% dichloromethane up to 10% methanol/90% dichloromethane in 30 minutes. Concentration of the product containing fractions gave (S)-2-{(R)-2-amino-2-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetylamino}-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide (490 mg, 87%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. extractionthen extracted with dichloromethane (three times)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe residue purified by chromatography over silica gel gradient
  7. washeluted from 100% dichloromethane up to 10% methanol/90% dichloromethane in 30 minutes
  8. additionConcentration of the product containing fractions

Sources & evidence

ORD record
ord-cc67ddf89bed49b7a70b37e2ab24ccbe
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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