Diisopropylethylamine → 2-[3-((1R,2R)-1-Benzyl-2-butoxycarbonyl-2-hydroxy-ethylcarbamoyl)-propyl]-benzoic Acid

HRID 2361125Notes

Reaction equation

HRID 2361125 reaction equation
C(O[C:6]([NH:8][C@H:9]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@@H:10]([OH:14])[C:11]([OH:13])=[O:12])=[O:7])(C)(C)C.C([CH2:25][CH2:26][CH2:27][C:28]1[CH:36]=[CH:35][CH:34]=[CH:33][C:29]=1[C:30]([OH:32])=[O:31])(O)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=N[C:56]2[CH:57]=[CH:58]C=N[C:55]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>Cl.O1CCOCC1.C(Cl)Cl.C(O)CCC>[CH2:15]([C@@H:9]([NH:8][C:6]([CH2:25][CH2:26][CH2:27][C:28]1[CH:36]=[CH:35][CH:34]=[CH:33][C:29]=1[C:30]([OH:32])=[O:31])=[O:7])[C@H:10]([C:11]([O:13][CH2:55][CH2:56][CH2:57][CH3:58])=[O:12])[OH:14])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

9

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 124220832-(3-Carboxypropyl)benzoic acidHCID 16211299(2R,3R)-3-(Boc-amino)-2-hydroxy-4-phenylbutyric acid

Product 1

HCID 710739122-[3-((1R,2R)-1-Benzyl-2-butoxycarbonyl-2-hydroxy-ethylcarbamoyl)-propyl]-benzoic AcidYield 99%

Reagents, catalysts & solvents 4

HCID 2631-ButanolSolventHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

(2R,3R)-3-t-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyric acid (244 mg, 827 μmol, 1.0 eq.) and 1-butanol (4 mL) were combined in 4 M HCl in 1,4-dioxane (1 mL), and stirred for 2 hours at 60° C. The solvent was evaporated and the reaction mixture was azeotroped with toluene. 2-(3-Carboxy-propyl)benzoic acid (160 mg, 790 μmol, 1.0 eq.), DIPEA (439 μL, 3.2 eq.), and HATU (300 mg, 788 μmol, 1.0 eq.) were combined in DCM (20 mL) and stirred for 5 minutes at room temperature. This mixture was then added to the azeotroped mixture and stirred for 1 hour. The solvent was evaporated and the crude material was dissolved in AcOH (2 mL) and purified using preparative HPLC to yield the title compound (80 mg, 99% purity). MS m/z [M+H]+ calc'd for C25H31NO6, 442.22. found 442.2.

Workup

  1. customThe solvent was evaporated
  2. customthe reaction mixture was azeotroped with toluene
  3. stirringstirred for 5 minutes at room temperature
  4. additionThis mixture was then added to the azeotroped mixture
  5. stirringstirred for 1 hour
  6. customThe solvent was evaporated
  7. dissolutionthe crude material was dissolved in AcOH (2 mL)
  8. custompurified

Sources & evidence

ORD record
ord-6b43ea0142bb483ea6a39976fa1caa9a
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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