Iodine → HCID 58237928, compound

HRID 1192922Notes

Reaction equation

HRID 1192922 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]([CH2:18][CH2:19][C:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[O:21])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[CH:4][CH:3]=1.II.Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34]>C1COCC1.[Zn]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([N:10]([C:11]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:17])[CH2:18][CH2:19][C:20]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)([OH:21])[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:9])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 807IodineHCID 7748Ethyl bromoacetateHCID 58200034HCID 58200034, compound

Product 1

HCID 58237928HCID 58237928, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of (S)-tert-butyl 1-(4-bromophenyl)ethyl(3-(4-fluorophenyl)-3-oxopropyl)carbamate (13 g, 28.9 mmol) and zinc powder (9.4 g, 0.144 mol) in THF (200 mL) at rt was added iodine (4.40 g, 0.173 mol) and ethyl bromoacetate (9.7 g, 57.7 mmol). The mixture was heated at reflux for 2 h, and quenched by addition of water. The mixture was filtered through a celite pad, the filtrate was extracted with EtOAc. The organic phase was concentrated to give the crude product, which was purified by column chromatography to afford ethyl 5-(((S)-1-(4-bromophenyl)ethyl)(tert-butoxycarbonyl)amino)-3-(4-fluorophenyl)-3-hydroxypentanoate (4.8 g, 31%). 1H NMR (CDCl3): δ 1.02 (t, 3H), 1.29-1.41 (m, 12H), 1.88 (m, 1H), 2.51-2.73 (m, 3H), 2.99 (m, 1H), 3.96 (q, 2H), 4.03 (m, 1H), 4.36 (m, 1H), 4.77 (m, 1H), 5.33 (m, 1H), 6.88-6.96 (m, 4H), 7.11 (m, 2H), 7.24 (m, 1H), 7.36 (m, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2 h
  3. customquenched by addition of water
  4. filtrationThe mixture was filtered through a celite pad
  5. extractionthe filtrate was extracted with EtOAc
  6. concentrationThe organic phase was concentrated
  7. customto give the crude product, which
  8. customwas purified by column chromatography

Sources & evidence

ORD record
ord-8e559fe8e7674cde981eae2b157d4872
Source dataset
uspto-grants-2014_03
Patent number
US08680281B2

Reaction notes

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