Cesium carbonate → HCID 59752981, compound

HRID 1909718Notes

Reaction equation

HRID 1909718 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+]>O1CCOCC1.CCOC(C)=O.O.Cl.CN(C)CC(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 3

HCID 10796Cesium carbonateHCID 27764185-(4-Bromophenyl)-1,3-oxazoleHCID 69004112(S)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59752981HCID 59752981, compoundYield 99.9%

Reagents, catalysts & solvents 4

HCID 75605N,N-Dimethylglycine hydrochlorideCatalystHCID 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 at 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 vacuo, 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 vacuo, residue
  9. customwas triturated with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-280458027d6c4c888f8d24e5ed5b56da
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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