Diisopropylethylamine → 5'-[(1R,2R)-2-Carboxy-1-(2-chlorobenzyl)-2-hydroxy-ethylcarbamoyl]-2',3'-difluoro-biphenyl-2-carb oxylic Acid

HRID 2361117Notes

Reaction equation

HRID 2361117 reaction equation
C([O:5][C:6]([C:8]1[C:9]([C:14]2[C:19]([F:20])=[C:18]([F:21])[CH:17]=[C:16]([C:22]([OH:24])=O)[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])(C)(C)C.C([O:27][C:28](=[O:41])[C@H:29]([OH:40])[C@H:30]([NH2:39])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:38])C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:28]([C@H:29]([OH:40])[C@H:30]([NH:39][C:22]([C:16]1[CH:17]=[C:18]([F:21])[C:19]([F:20])=[C:14]([C:9]2[C:8]([C:6]([OH:5])=[O:7])=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:15]=1)=[O:24])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:38])([OH:41])=[O:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71073615(2R,3R)-3-Amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid ethyl esterHCID 710738195',6'-Difluoro-biphenyl-2,3'-dicarboxylic acid 2-t-butyl ester

Product 1

HCID 710737975'-[(1R,2R)-2-Carboxy-1-(2-chlorobenzyl)-2-hydroxy-ethylcarbamoyl]-2',3'-difluoro-biphenyl-2-carb oxylic AcidYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5′,6′-Difluoro-biphenyl-2,3′-dicarboxylic acid 2-t-butyl ester (60 mg, 180 μmol, 1.0 eq.), (2R,3R)-3-amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid ethyl ester (46.3 mg, 180 μmol, 1.0 eq.), DIPEA (94 μL), and HATU (68.4 mg, 180 μmol) were combined in DCM (2 mL) and was stirred for 45 minutes at room temperature. The reaction was quenched with saturated NH4Cl and extracted with DCM, dried and evaporated. 1:1 DCM:TFA (0.5 mL each) was added and the mixture was stirred for 30 minutes. The solvent was evaporated under vacuum. THF (2 mL) and 10N NaOH (0.3 mL) were added and the mixture was stirred for 2 hours. The reaction was quenched with AcOH and the product was purified by preparative HPLC to yield the title compound (5.8 mg, 97% purity). MS m/z [M+H]+ calc'd for C24H18ClF2NO6, 490.08. found 491.

Workup

  1. customThe reaction was quenched with saturated NH4Cl
  2. extractionextracted with DCM
  3. customdried
  4. customevaporated
  5. addition1:1 DCM:TFA (0.5 mL each) was added
  6. stirringthe mixture was stirred for 30 minutes
  7. customThe solvent was evaporated under vacuum
  8. additionTHF (2 mL) and 10N NaOH (0.3 mL) were added
  9. stirringthe mixture was stirred for 2 hours
  10. customThe reaction was quenched with AcOH
  11. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-f3b69ef0e1584d7fa7c429ae86e0fdde
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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