Iodine → HCID 86689664, compound

HRID 1775814Notes

Reaction equation

HRID 1775814 reaction equation
II.[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16]I)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]=[C:27]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:32][CH:31]=3)[O:28][CH:29]=2)=[CH:21][CH:20]=1.C1COCC1>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[C:3]([O:7][C:8]([NH:10][C@@H:11]([CH2:16][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[N:26]=[C:27]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])=[CH:34][CH:35]=3)[O:28][CH:29]=2)=[CH:23][CH:24]=1)[C:12]([O:14][CH3:15])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

9

Reactant 4

HCID 807Iodine2×HCID 8028TetrahydrofuranHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 86689662HCID 86689662, compound

Product 1

HCID 86689664HCID 86689664, compoundYield 66.1%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To zinc (104 mg, 1.59 mmol) stirring in DMF (1.5 mL) was added iodine (20.2 mg, 0.08 mmol). After the color disappeared, (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (175 mg, 0.53 mmol) and further iodine (20.2 mg, 0.08 mmol) were added. After 30 min, the mixture was de-gassed by bubbling through N2 then treated with 4-(4-bromophenyl)-2-(4-(heptyloxy)phenyl)oxazole (220 mg, 0.53 mmol), Pd2dba3 (12.2 mg, 0.01 mmol) and dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (10.9 mg, 0.03 mmol) followed by THF (1 mL). The reaction mixture was heated to 50° C. for 2 h, cooled to room temperature and purified by column chromatography (gradient of 15-95% EA in iso-hexanes) to afford 188 mg (65%) of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(2-(4-(heptyloxy)phenyl)oxazol-4-yl)phenyl)propanoate. LCMS-ESI (m/z) calculated for C31H40N2O6: 536.6. found 537.0 [M+H]+, tR=3.72 min. (Method 11).

Workup

  1. customthe mixture was de-gassed
  2. customby bubbling through N2
  3. temperaturecooled to room temperature
  4. custompurified by column chromatography (gradient of 15-95% EA in iso-hexanes)

Sources & evidence

ORD record
ord-4ff83674ee5b49df8d6773ce1b16e298
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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