Sodium Hydroxide → HCID 58286949, compound

HRID 1962392Notes

Reaction equation

HRID 1962392 reaction equation
[CH:1]1([C@H:5]([NH:13][C:14]([CH2:16][C:17]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[C:18]=2[C:19]([OH:21])=[O:20])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1.[C:28](C1C2C=C(F)C=C(F)C=2C(=O)OC=1N[C@@H](C1CCC1)C1C=CC=C(F)C=1)(=[O:30])[CH3:29].C1([C@H](NC(C2C3C=C(F)C=C(F)C=3C(=O)OC=2C)=O)C2C=CC=C(F)C=2)CCC1.[OH-].[Na+]>C(OC(=O)C)(=O)C.O1CCCC1>[CH:1]1([C@H:5]([NH:13][C:14]([CH:16]([C:17]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[C:18]=2[C:19]([OH:21])=[O:20])[C:28](=[O:30])[CH3:29])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 58286963HCID 58286963, compoundHCID 67072794HCID 67072794, compoundHCID 67220666HCID 67220666, compound

Product 1

HCID 58286949HCID 58286949, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 7918Acetic AnhydrideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-({[(S)-Cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-methyl)-4,6-difluoro-benzoic acid (3.4 g, 9.0 mmol in acetic anhydride (60 mL) was stirred at 100° C. overnight then evaporated and co-evaporated with toluene twice in vacuo to give a mixture of 4-acetyl-3-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amino}-6,8-difluoro-2-benzopyran-1-one and 6,8-difluoro-3-methyl-1-oxo-1H-2-benzopyran-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide. The obtained residue was dissolved in tetrahydrofuran (15 mL), allowed to cool on an ice-water bath and 2M aqueous NaOH (18 mL) was added. The cold bath removed and the reaction mixture was stirred for 30 min. The obtained mixture was diluted with water (20 mL) and extracted with isopropyl acetate (40 mL) which was washed with water (40 mL). The combined aqueous phase was cooled on ice bath and the pH was adjusted to 1 with conc. HCl. The title product was separated by extraction with isopropylacetate (2×40 mL) and purified by flash chromatography (50 g SiO2, the product was eluted with 1:1 ethyl acetate-heptane, 1.58 g, yield 42%). LC-MS (m/z) 420.6 (MH+); tR=1.35.

Workup

  1. customthen evaporated
  2. customto give
  3. temperatureto cool on an ice-water bath
  4. customThe cold bath removed
  5. additionThe obtained mixture was diluted with water (20 mL)
  6. extractionextracted with isopropyl acetate (40 mL) which
  7. washwas washed with water (40 mL)
  8. temperatureThe combined aqueous phase was cooled on ice bath
  9. customThe title product was separated by extraction with isopropylacetate (2×40 mL)
  10. custompurified by flash chromatography (50 g SiO2
  11. washthe product was eluted with 1:1 ethyl acetate-heptane, 1.58 g, yield 42%)

Sources & evidence

ORD record
ord-6a081381a1f04f7e9b6b3dbaa3dbd23d
Source dataset
uspto-grants-2013_04
Patent number
US08415356B2

Reaction notes

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