Triethylamine → Setafrastat

HRID 710032Notes

Reaction equation

HRID 710032 reaction equation
[F:1][C:2]([F:17])([C:6]1([OH:16])[CH2:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]([CH3:15])([CH3:14])[CH2:7]1)[C:3]([OH:5])=O.CCN(CC)CC.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH2:32][C:33]2[O:37][N:36]=[C:35]([C@@H:38]3[CH2:42][CH2:41][CH2:40][NH:39]3)[CH:34]=2)[CH:26]=1.C(=O)(O)[O-].[Na+]>C1COCC1.ClC(OCC)=O>[F:17][C:2]([F:1])([C:6]1([OH:16])[CH2:11][C:10]([CH3:13])([CH3:12])[CH2:9][C:8]([CH3:15])([CH3:14])[CH2:7]1)[C:3]([N:39]1[CH2:40][CH2:41][CH2:42][C@H:38]1[C:35]1[CH:34]=[C:33]([CH2:32][O:31][C:27]2[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=2)[O:37][N:36]=1)=[O:5]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 68542826Difluoro(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acidHCID 86706744(S)-5-((Pyridin-3-yloxy)methyl)-3-(pyrrolidin-2-yl)isoxazole

Product 1

HCID 73672050SetafrastatYield 58.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 10928Ethyl chloroformateSolvent

Procedure

To a solution of 2,2-difluoro-2-(1-hydroxy-3,3,5,5-tetramethylcyclohexyl)acetic acid (3.192 g) and Et3N (4.44 mL) in THF (100 mL), ethyl chloroformate (1.12 mL) was added at room temperature and the mixture was stirred for an hour. To the reaction mixture, a THF (50 mL) solution of the compound (2.607 g) obtained in Example 2-(3) was added dropwise at room temperature and the mixture was stirred at room temperature for 64 hours. To the reaction mixture, saturated aqueous sodium bicarbonate (200 mL) was added and the organic layer extracted with AcOEt (200 mL) was washed with brine (200 mL), dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by NH-form silica gel chromatography (AcOEt/hexane); the resulting compound was recrystallized (Et2O/pentane) to give the titled compound (2.969 g, colorless powder.)

Workup

  1. stirringthe mixture was stirred at room temperature for 64 hours
  2. extractionthe organic layer extracted with AcOEt (200 mL)
  3. washwas washed with brine (200 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas further purified by NH-form silica gel chromatography (AcOEt/hexane)
  9. customthe resulting compound was recrystallized (Et2O/pentane)

Sources & evidence

ORD record
ord-d1482ff9c6944c54b53d738c9e260271
Source dataset
uspto-grants-2015_11
Patent number
US09181229B2

Reaction notes

Loading…