Water → HCID 57476712, compound

HRID 1044539Notes

Reaction equation

HRID 1044539 reaction equation
BrCCBr.[C:5]([O:9][C:10]([N:12]1[CH2:15][CH:14](I)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].FC(F)(F)S(O[C:23]1[CH:32]=[CH:31][C:30]2[CH2:29][CH2:28][CH:27]([NH:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:26]([CH2:39][C:40]3[CH:45]=[CH:44][C:43](Cl)=[C:42]([Cl:47])[CH:41]=3)[C:25]=2[CH:24]=1)(=O)=O.O>CC(N(C)C)=O.[Zn].[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:5]([O:9][C:10]([N:12]1[CH2:15][CH:14]([C:23]2[CH:32]=[CH:31][C:30]3[CH2:29][CH2:28][CH:27]([NH:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:26]([CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([Cl:47])[CH:41]=4)[C:25]=3[CH:24]=2)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

9

Reactant 4

HCID 962WaterHCID 78391,2-DibromoethaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 46870536HCID 46870536, compound

Product 1

HCID 57476712HCID 57476712, compoundYield 86.3%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent3×

Conditions

Temperature
67.5 °C

Procedure

A suspension of zinc powder (152 mg, 2.3 mmol) in 1 ml of DMA in a dry flask was heated under N2 to 65-70° C. A mixture of TMS-CI (28 mg, 0.26 mmol) and 1,2-dibromoethane (49 mg, 0.26 mmol) was added dropwise, stirred for 30 min, followed by slow (15 min) addition of 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (510 mg, 1.8 mmol) in 1 ml DMA. The reaction was cooled slowly (3 h) to room temperature, added to a mixture of 8-(3,4-chlorobenzyl)-7-[(ethoxycarbonyl)amino)-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (633 mg, 1.3 mmol, prepared in analogy to example 29), CuI (74 mg, 0.39 mmol) and PdCl2(dppf) (63 mg, 0.08 mmol) in 4 ml DMA preheated to 70° C. and stirred for 7 h at 70° C. Water and MTB (1:1 20 ml) were added and the resulting mixture filtered. The organic layer was separated, dried (Na2SO4) and the solvent evaporated. Purification by chromatography afforded 560 mg of product (white foam).

Workup

  1. additionwas added dropwise
  2. temperatureThe reaction was cooled slowly (3 h) to room temperature
  3. custompreheated to 70° C.
  4. stirringstirred for 7 h at 70° C
  5. filtrationthe resulting mixture filtered
  6. customThe organic layer was separated
  7. dry with materialdried (Na2SO4)
  8. customthe solvent evaporated
  9. customPurification by chromatography

Sources & evidence

ORD record
ord-b013d68bcc324860b7d206d6a5061479
Source dataset
uspto-grants-2013_10
Patent number
US08563617B2

Reaction notes

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