Hydrochloric Acid → HCID 68999209, compound

HRID 750070

Reaction equation

HRID 750070 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]2[O:33][CH:32]=[N:31][CH:30]=2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O.Cl>O1CCOCC1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:23]2[CH:24]=[CH:25][C:26]([C:29]3[O:33][CH:32]=[N:31][CH:30]=3)=[CH:27][CH:28]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 27764185-(4-Bromophenyl)-1,3-oxazoleHCID 68999591(R)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68999209HCID 68999209, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
98 °C

Procedure

To a 25 mL pressure resistant vial which contained a solution of (R)-2-(4-hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (147 mg, 0.5 mmol) and 5-(4-bromo-phenyl)-oxazole (170 mg, 0.75 mmol) in anhydrous dioxane (4 mL) were added cesium carbonate (300 mg, 1.5 mmol) and N,N-dimethylglycine.HCl (25 mg, 0.66 mmol) at rt. The reaction mixture was flushed with argon and Copper (I) iodide (14 mg, 0.06 mmol) was added. The vial was sealed and the reaction mixture was stirred at 98° C. for 72 h. After cooling to rt, the mixture was poured onto 50 mL ice-water solution and this solution was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (2×20 mL), brine (20 mL) and dried over anhydrous Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford title product (145 mg, 65%).

Workup

  1. customat rt
  2. additionwas added
  3. customThe vial was sealed
  4. temperatureAfter cooling to rt
  5. extractionthis solution was extracted with EtOAc (3×20 mL)
  6. washThe combined organic layers were washed with water (2×20 mL), brine (20 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe solvent was removed in vacuo
  9. customto obtain the crude product which
  10. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-82abdb4614dd42e882a5e646b8a797af
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Linked notes

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