Ethanol → HCID 59363810, compound

HRID 1430647Notes

Reaction equation

HRID 1430647 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][C:5]1[N:6]=[C:7]([NH:11][C:12](=[O:34])[C:13]([O:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH3:14])[S:8][C:9]=1[Cl:10].C(O)C.O.[OH-].[Li+]>C1COCC1>[Cl:10][C:9]1[S:8][C:7]([NH:11][C:12](=[O:34])[C:13]([O:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=2[F:33])([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[CH3:14])=[N:6][C:5]=1[CH2:4][C:3]([OH:35])=[O:2]

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 3939Lithium HydroxideHCID 59363835HCID 59363835, compound

Product 1

HCID 59363810HCID 59363810, compoundYield 33.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {5-Chloro-2-[2-(2,4-difluoro-phenoxy)-2-(4-methanesulfonyl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid methyl ester (0.03 g, 0.05 mmol) in THF:Ethanol:water (1 ml+0.3 ml+0.3 ml) was added lithium hydroxide (0.0046 g, 0.11 mmol). The resulting mixture was stirred for 5 hours at room temperature followed by removal of solvent under reduced pressure. The residue was suspended in water (15 ml), extracted with ethyl acetate to remove impurities. The aqueous layer was acidified with 1N HCl (0.5 ml) and extracted with ethyl acetate (2×10 ml), This ethyl acetate layer was washed with water (15 ml), brine (20 ml), dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to give solid product {5-Chloro-2-[2-(2,4-difluoro-phenoxy)-2-(4-methanesulfonyl-phenyl)-propionylamino]-thiazol-4-yl}-acetic acid (9 mg). 1H NMR (400 MHz, CDCl3): δ 1.85 (s, 3H), 3.07 (s, 3H), 3.72 (s, 2H), 6.64-6.69 (m, 2H), 6.89-6.91 (m, 1H), 7.84 (d, J=8.4 Hz, 2H), 8.00 (d, J=8.8 Hz, 2H). MS (EI) m/z: 530.70 (M+1), mp: 109-111° C.

Workup

  1. customfollowed by removal of solvent under reduced pressure
  2. extractionextracted with ethyl acetate
  3. customto remove impurities
  4. extractionextracted with ethyl acetate (2×10 ml)
  5. washThis ethyl acetate layer was washed with water (15 ml), brine (20 ml)
  6. dry with materialdried over anhydrous sodium sulfate and solvent
  7. customwas removed under reduced pressure

Sources & evidence

ORD record
ord-88017d8268214374b1a4e8d3522a52d1
Source dataset
uspto-grants-2015_01
Patent number
US08940900B2

Reaction notes

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