Triethylamine → Rac-(cis)-2-[3-(2',4'-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid

HRID 547852Notes

Reaction equation

HRID 547852 reaction equation
C([O:5][C:6](=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=3[F:29])=[CH:18][CH:17]=2)[CH:9]=1)(C)(C)C.C(N(CC)CC)C.[C@@H:38]1(C(O)=O)[CH2:42][CH2:41][CH2:40][C@@H:39]1[C:43]([OH:45])=[O:44].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CCOC(C)=O.CN(C=O)C>[F:29][C:23]1[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:22]=1[C:19]1[CH:18]=[CH:17][C:16]([O:15][CH2:14][C:10]2[CH:9]=[C:8]([NH:7][C:6]([C@H:38]3[CH2:42][CH2:41][CH2:40][C@H:39]3[C:43]([OH:45])=[O:44])=[O:5])[CH:13]=[CH:12][CH:11]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 727374cis-Cyclopentane-1,2-dicarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58287788[3-(2',4'-Difluoro-biphenyl-4-yloxymethyl)-phenyl]-carbamic acid tert-butyl ester

Product 1

HCID 52920222Rac-(cis)-2-[3-(2',4'-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acidYield 53.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

[3-(2′,4′-Difluoro-biphenyl-4-yloxymethyl)-phenyl]-carbamic acid tert-butyl ester (111 mg, 0.269 mmol) was stirred in 5 mL EtOAc (saturated with HCl) at RT for 45 min. The mixture was evaporated, re-evaporated from EtOAc and pumped under high vacuum to give a solid. The crude product was dissolved in DMF (2 mL). To this solution, chilled in an ice bath, was added triethylamine (150 uL, 1.08 mmol), (cis)-cyclopentane-1,2-dicarboxylic acid (64 mg, 0.404 mmol) and HATU (154, 0.404 mmol) was added and then let stir at RT for 30 min. The reaction mixture was diluted with EtOAc (25 mL), washed with 1N HCl (10 mL), H2O (10 mL), saturated NaCl (10 mL), dried over MgSO4, filtered and evaporated to give a white solid. The crude product was purified by flash chromatography with a 0-55% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in hexanes to yield 64.8 mg of rac-(cis)-2-[3-(2′,4′-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid as a white solid.

Workup

  1. customThe mixture was evaporated
  2. customre-evaporated from EtOAc
  3. customto give a solid
  4. temperatureTo this solution, chilled in an ice bath
  5. additionwas added
  6. washwashed with 1N HCl (10 mL), H2O (10 mL), saturated NaCl (10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto give a white solid
  11. customThe crude product was purified by flash chromatography with a 0-55% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in hexanes

Sources & evidence

ORD record
ord-bc424c5a0ec04fc6ace5292d4e36f0bb
Source dataset
uspto-grants-2011_05
Patent number
US07939569B1

Reaction notes

Loading…