Iodine → 4-(4-(4-(Heptyloxy)phenyl)thiazol-2-yl)phenyl propanoate

HRID 716400Notes

Reaction equation

HRID 716400 reaction equation
II.C(OC(N[C@@H:11]([CH2:16]I)[C:12]([O:14][CH3:15])=[O:13])=O)(C)(C)C.BrC1[CH:24]=[CH:23][C:22]([C:25]2[S:26][CH:27]=[C:28]([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)[N:29]=2)=[CH:21][CH:20]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>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]>[C:12]([O:14][C:15]1[CH:24]=[CH:23][C:22]([C:25]2[S:26][CH:27]=[C:28]([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)[N:29]=2)=[CH:21][CH:20]=1)(=[O:13])[CH2:11][CH3:16]

Participants

8

Reactant 4

HCID 807Iodine2×HCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 866896652-(4-Bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole

Product 1

HCID 1317316654-(4-(4-(Heptyloxy)phenyl)thiazol-2-yl)phenyl propanoate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a stirring suspension of zinc (228 mg, 3.49 mmol) in DMF (2 mL) was added diiodine (44 mg, 0.17 mmol). When the color was discharged, (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (382 mg, 1.16 mmol) and further diiodine (44.2 mg, 0.17 mmol) were added. After stirring at RT for 30 min, the reaction mixture was de-gassed by bubbling through N2 then 2-(4-bromophenyl)-4-(4-(heptyloxy)phenyl)thiazole (500 mg, 1.16 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (23.8 mg, 0.06 mmol), Pd2dba3 (26 mg, 0.03 mmol) and DMF (2 mL) were added. The reaction mixture was heated to 50° C. for 3 h, cooled and purified by column chromatography (10-80% EA in iso-hexanes) to afford 620 mg (96%) of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-(4-(4-(heptyloxy)phenyl) thiazol-2-yl)phenyl propanoate. LCMS-ESI (m/z) calculated for C31H40N2O5S: 552.3; no ion observed, tR=3.37 min. (Method 4).

Workup

  1. customthe reaction mixture was de-gassed
  2. customby bubbling through N2
  3. temperatureThe reaction mixture was heated to 50° C. for 3 h
  4. temperaturecooled
  5. custompurified by column chromatography (10-80% EA in iso-hexanes)

Sources & evidence

ORD record
ord-44d0124fe4f34e3bb5ec85fa4d70d0ea
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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