Triethylamine → HCID 69034550, compound

HRID 225961Notes

Reaction equation

HRID 225961 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][NH:6][C@@H:5]([CH2:8][C:9]([OH:11])=[O:10])[CH2:4]1.C(N(CC)CC)C.[C:19]1([C:25]2[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][CH:26]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O.O1CCCC1>[C:25]1([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:26]=[CH:27][C:28]([C:29]([N:6]2[CH2:7][C@H:3]([OH:2])[CH2:4][C@H:5]2[CH2:8][C:9]([OH:11])=[O:10])=[O:30])=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 841514-Phenylbenzoyl chlorideHCID 69039742HCID 69039742, compound

Product 1

HCID 69034550HCID 69034550, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of commercial [(2R,4R)-4-hydroxypyrrolidin-2-yl]acetic acid hydrochloride (5.03 g, 27.69 mmol), triethylamine (11.32 g, 110.77 mmol) in water (16.5 ml) and tetrahydrofuran (25 ml) at 0° C. under argon was added drop wise a solution of the 4-phenyl-benzoyl chloride in dry tetrahydrofuran (25 ml). The reaction was allowed to warm to RT and stirred overnight The reaction mixture was concentrated and the crude product was acidified under stirring at 5° C. adding 100 ml of HCl 1N. The white suspension was stirred at 5° C. for 10 minutes, filtered off under vacuum, rinsed with HCl 1N and water. After drying under vacuum the still wet white solid was taken up in 14 ml of tetrahydrofuran and brought to reflux until dissolution, and hexane was added to precipitate the solid. The whole was allowed to cool down to RT under stirring for 5 minutes and was filtered off and rinsed with hexane to give [(2S,4R)-1-(biphenyl-4-ylcarbonyl)-4-hydroxypyrrolidin-2-yl] acetic acid as a white powder (4.344 g). Yield: 72%. HPLC purity: 84%

Workup

  1. concentrationwas concentrated
  2. stirringunder stirring at 5° C.
  3. additionadding 100 ml of HCl 1N
  4. stirringThe white suspension was stirred at 5° C. for 10 minutes
  5. filtrationfiltered off under vacuum
  6. washrinsed with HCl 1N and water
  7. customAfter drying under vacuum the still wet white solid
  8. temperatureto reflux until dissolution, and hexane
  9. additionwas added
  10. customto precipitate the solid
  11. temperatureto cool down to RT
  12. stirringunder stirring for 5 minutes
  13. filtrationwas filtered off
  14. washrinsed with hexane

Sources & evidence

ORD record
ord-02e944ccee814bf98592f51ed1c7adb1
Source dataset
uspto-grants-2009_07
Patent number
US07557136B2

Reaction notes

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