Hydrochloric Acid → HCID 178428305, compound

HRID 928135Notes

Reaction equation

HRID 928135 reaction equation
[OH:1][C:2]([C@H:27]1[CH2:32][CH2:31][C@H:30]([C:33]([O:35]CCCC)=[O:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3].[OH-].[Na+].Cl>CO.O.C(OCC)(=O)C>[OH:1][C@:2]([C@H:27]1[CH2:32][CH2:31][C@H:30]([C:33]([OH:35])=[O:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3].[OH:1][C@@:2]([C@H:27]1[CH2:32][CH2:31][C@H:30]([C:33]([OH:35])=[O:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3]

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 178451151HCID 178451151, compound

Product 2

HCID 178428305HCID 178428305, compoundHCID 178428306HCID 178428306, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of butyl trans-4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)-pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylate (600 mg, 1.066 mmol) in methanol (10.7 mL) was added sodium hydroxide (1.0 M in H2O, 2.13 mL, 2.13 mmol) and the reaction was heated overnight at 100° C. The reaction was then cooled to room temperature, acidified with HCl (1.0 M in H2O) to a pH of ˜3 and then diluted with water and ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated. The residue was purified and at the same time the enantiomers separated by supercritical fluid chromatography (Chiral OJ column, 35%:75% methanol/CO2 5.0 min run time) to yield trans-4-{(1R)-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid and trans-4-{(1S)-1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}cyclohexanecarboxylic acid. Characterization data for the faster eluting enantiomer (Rt=3.22 min): MS ESI calc'd. for C24H26F3N4O3S [M+H]+ 507. found 507. 1H NMR (500 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.83 (d, J=4.9, 1H), 7.99-7.92 (m, 2H), 7.45 (s, 1H), 7.27 (d, J=4.9, 1H), 7.14 (s, 1H), 5.82 (s, 1H), 2.31 (s, 3H), 2.10-1.95 (m, 1H), 1.95-1.73 (m, 2H), 1.72-1.58 (m, 1H), 1.58-1.50 (m, 1H), 1.47 (s, 3H), 1.32-1.11 (m, 4H), 1.10-0.94 (m, 1H). rhSyk=+++. The slower eluting enantiomer Rt=4.04 min. rhSyk=+++

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. customThe organic layer was separated
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified and at the same time the enantiomers
  7. customseparated by supercritical fluid chromatography (Chiral OJ column, 35%:75% methanol/CO2 5.0 min run time)

Sources & evidence

ORD record
ord-870fa2bc0b3b478391ca6d9f938e7bdc
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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