Cesium carbonate → HCID 59752981, compound

HRID 750030

Reaction equation

HRID 750030 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][CH:11]=[N:10][CH:9]=2)=[CH:4][CH:3]=1.C(OC([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.O>[NH:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:12][CH:11]=[N:10][CH:9]=3)=[CH:4][CH:3]=2)=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 27764185-(4-Bromophenyl)-1,3-oxazoleHCID 69004112HCID 69004112, compound

Product 1

HCID 59752981HCID 59752981, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent3×

Conditions

Temperature
85 °C

Procedure

To a solution of 5-(4-bromophenyl)-1,3-oxazole (224 mg, 1.0 mmol) in dioxane (2 mL) was added (S)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (440 mg, 1.5 mmol) in dioxane (2 mL) and cesium carbonate (651 mg, 2.0 mmol). The vessel was purged with nitrogen for 15 min before N,N-dimethylglycine hydrochloride (12.5 mg, 0.09 mmol) in dioxane (1 mL) and Cu(I) iodide (6 mg, 0.03 mmol) were added. The resulted mixture was stirred it 85° C. for 16 h. It was then diluted with EtOAc and water, organic layer was separated, washed with water, brine, dried over anhydrous MgSO4 and concentrated in vacuo to dark brownish oil. The crude mixture was purified by silica gel flash chromatography (10% EtOAc/Hexane) before treating it with 4M HCl in dioxane (5 mL) at rt for 1 h. Solvent was removed in residue was triturated with ether and dried under vacuum to give the product, as white solid (336 mg, 90%): MS; m/z 337.4 M+H), 1H NMR (400 MHz, DMSO-d6); δ 1.71-2.15 (m, 4H), 3.18-3.25 (m, 2H), 3.88-3.91 (m, 1H), 4.12-4.17 (m, 1H), 4.23-4.27 (m, 1H), 7.00-7.10 (m, 6H), 7.59 (s, 1H), 7.71 (dd, 2H, J1=6.8 Hz, J2=2.4 Hz, 8.41 (s, 1H), 9.04 (br, 1H), 9.6 (br, 1H); HPLC (UV); 99%

Workup

  1. additionwere added
  2. customwas separated
  3. washwashed with water, brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo to dark brownish oil
  6. customThe crude mixture was purified by silica gel flash chromatography (10% EtOAc/Hexane)
  7. additionbefore treating it with 4M HCl in dioxane (5 mL) at rt for 1 h
  8. customSolvent was removed in residue
  9. customwas triturated with ether
  10. customdried under vacuum
  11. customto give the product

Sources & evidence

ORD record
ord-0159d56757fd4fb7855dbcec5ac9adc8
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Linked notes

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