Hydrochloric Acid → HCID 90418257, compound

HRID 2177391Notes

Reaction equation

HRID 2177391 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[CH:21]([CH2:25][C:26]([O:28]CC)=[O:27])[CH2:20][CH2:19]4)=[C:12]([C:31]([F:34])([F:33])[F:32])[S:11][N:10]=2)=[CH:5][CH:4]=1)[CH3:2].O1CCCC1.[Li+].[OH-].Cl>O>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([CH2:14][O:15][C:16]3[CH:17]=[C:18]4[C:22](=[CH:23][CH:24]=3)[CH:21]([CH2:25][C:26]([OH:28])=[O:27])[CH2:20][CH2:19]4)=[C:12]([C:31]([F:33])([F:32])[F:34])[S:11][N:10]=2)=[CH:5][CH:4]=1)[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 90418851HCID 90418851, compound

Product 1

HCID 90418257HCID 90418257, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

Into a 50-mL round-bottom flask, was placed ethyl 2-(5-[[3-(4-ethylphenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-2,3-dihydro-1H-inden-1-yl)acetate (220 mg, 0.45 mmol, 1.00 equiv), tetrahydrofuran (5 mL), water (4 mL), LiOH (97 mg, 4.05 mmol, 9.01 equiv). The resulting solution was stirred overnight at 30° C. The pH value of the solution was adjusted to 2 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 3×3 mL of ethyl acetate and the organic layers combined and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (waters2767-16): Column, SunFire Prep C18,19*150 mm 5 umH PrepC-001(T)18600256819513816414 04; mobile phase, PhaseA:water with 0.05% NH4HCO3, PhaseB:CH3CN(50% CH3CN up to 100% in 10 min, hold 100% in 1.9 min, down to 50% in 0.1 min, hold 50% in 1.9 min); Detector, UV220&254 nm. This resulted in 18 mg (19%) of 2-(5-[[3-(4-ethylphenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-2,3-dihydro-1H-inden-1-yl)acetic acid as light yellow oil. 1H NMR: (CDCl3, 400 MHz): δ 7.65 (d, J=8.0 Hz, 2H), 7.30 (d, J=4.8 Hz, 2H), 7.17 (d, J=8.0 Hz, 1H), 6.79-6.85 (m, 2H), 5.05 (s, 2H), 3.58-3.61 (m, 1H), 2.82-2.98 (m, 3H), 2.69-2.75 (m, 2H), 2.44-2.54 (m, 2H), 1.79-1.88 (m, 1H), 1.28 (t, J=7.5 Hz, 3H). Mass spectrum (ESI, m/z): Calcd. for C24H22F3NO3S, 460.1 (M−H). found 460.1.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 3×3 mL of ethyl acetate
  3. concentrationconcentrated under vacuum
  4. customThe crude product was purified by Prep-HPLC with the following conditions (waters2767-16)
  5. waitmobile phase, PhaseA:water with 0.05% NH4HCO3, PhaseB:CH3CN(50% CH3CN up to 100% in 10 min
  6. customin 1.9 min
  7. waitdown to 50% in 0.1 min
  8. customin 1.9 min
  9. customThis resulted in 18 mg (19%) of 2-(5-[[3-(4-ethylphenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-2,3-dihydro-1H-inden-1-yl)acetic acid as light yellow oil

Sources & evidence

ORD record
ord-75da143b2ef84464bdcba4c6a95ca7c5
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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