Triethylamine → HCID 118114162, compound

HRID 2284847Notes

Reaction equation

HRID 2284847 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.CCN(CC)CC.[Br:18][CH2:19][C:20]1[CH:21]=[C:22]([S:26](Cl)(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1>C1COCC1.CCOC(C)=O>[Br:18][CH2:19][C:20]1[CH:21]=[C:22]([S:26]([N:6]2[CH2:7][CH2:8][CH2:9][C@H:5]2[C:4]([O:3][CH3:2])=[O:10])(=[O:28])=[O:27])[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 2733200methyl L-prolinate hydrochlorideHCID 234473893-(Bromomethyl)benzene-1-sulfonyl chloride

Product 1

HCID 118114162HCID 118114162, compoundYield 15.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (S)-proline methyl ester hydrochloride salt (1.6 g, 9.65 mmol) in THF (20 mL) was added Et3N (1.34 mL, 9.65 mmol) at 0° C. The reaction mixture was stirred at room temperature for 30 min and cooled back down to 0° C. 3-Bromomethyl-benzenesulfonyl chloride (2.6 g, 9.65 mmol) and Et3N (1.34 mL, 9.65 mmol) were then added to the slurry. The resulting mixture was stirred at room temperature for 3 h and then diluted with EtOAc (100 mL). The organic phase was washed with water (2×50 mL), brine (20 mL) and dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by chromatography via silica gel chromatography, eluting with 0-20% EtOAc in isohexane, to give 550 mg of (S)-methyl 1-((3-(bromomethyl)-phenyl)sulfonyl)pyrrolidine-2-carboxylate that was used in the next step without further purification. This residue was taken up in acetone (20 mL) and transferred to a microwave vial. (S)-tert-butyl ((3-hydroxyphenyl)(phenyl)methyl)carbamate (I8, 251 mg, 1.82 mmol) and K2CO3 (546 mg, 1.82 mmol) were added, and the mixture was heated to 130° C. under microwaves irradiation for 1 h. The mixture was stirred at room temperature for 18 h and partitioned between EtOAc (50 mL) and water (20 mL). The layers were separated and the aqueous phase extracted with EtOAc (3×30 mL). The combined organic phases were washed with brine (30 mL) and dried over MgSO4. The mixture was filtered and the solvent was removed in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% EtOAc in isohexane, to give the title compound (636 mg, 60%).

Workup

  1. temperaturecooled back down to 0° C
  2. stirringThe resulting mixture was stirred at room temperature for 3 h
  3. washThe organic phase was washed with water (2×50 mL), brine (20 mL)
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed in vacuo
  6. customthe crude product was purified by chromatography via silica gel chromatography
  7. washeluting with 0-20% EtOAc in isohexane

Sources & evidence

ORD record
ord-196ae68cb5894766ae8fa2cba68ff8d4
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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