Lithium Hydroxide → HCID 90418710, compound

HRID 2177195Notes

Reaction equation

HRID 2177195 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])[CH:5]=[C:6]([F:27])[C:7]=1[O:8][CH2:9][C:10]1[C:11]([C:19]2[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)=[N:12][S:13][C:14]=1[C:15]([F:18])([F:17])[F:16].COC1C=CC(C(N)=O)=CN=1.O1CCCC1.[Li+].[OH-]>O>[F:1][C:2]1[CH:3]=[C:4]([CH2:28][CH2:29][C:30]([OH:32])=[O:31])[CH:5]=[C:6]([F:27])[C:7]=1[O:8][CH2:9][C:10]1[C:11]([C:19]2[CH:20]=[N:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=2)=[N:12][S:13][C:14]=1[C:15]([F:16])([F:17])[F:18]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 2508106-METHOXYNICOTINAMIDEHCID 90418756HCID 90418756, compound

Product 1

HCID 90418710HCID 90418710, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

Into a 25-mL round-bottom flask, was placed ethyl 3-(3,5-difluoro-4-[[3-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]phenyl)propanoate (prepared according to the procedure following Example 1 step 1-5 using 6-methoxynicotinamide as starting material) (50 mg, 0.10 mmol, 1.00 equiv), tetrahydrofuran (1 mL), LiOH (50 mg, 2.09 mmol, 20.98 equiv), water (1 mL). The resulting solution was stirred overnight at 20° C. The resulting mixture was concentrated under vacuum. The pH value of the solution was adjusted to 6 with hydrogen chloride (2 mol/L). The solids were collected by filtration. The crude product (20 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Reversed Column, C18 silica gel; mobile phase, 0.05% TFA/ACN=1/4 increasing to 0.05% TFA/ACN=0/1 within 20 min; Detector, UV 254 nm. This resulted in 8.8 mg (18%) of 3-(3,5-difluoro-4-((3-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)phenyl)propanoic acid as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.51 (s, 1H), 8.06 (d, J=6.3 Hz, 1H), 6.80-6.89 (m, 3H), 5.19 (s, 2H), 3.96 (s, 3H), 2.83 (t, J=7.5 Hz, 2H), 2.56 (t, J=7.5 Hz, 2H). Mass spectrum (ESI, m/z): Calcd. for C20H15F5N2O4S, 475.1 (M+H). found 475.1.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. filtrationThe solids were collected by filtration
  4. customThe crude product (20 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  5. waitmobile phase, 0.05% TFA/ACN=1/4 increasing to 0.05% TFA/ACN=0/1 within 20 min
  6. customThis resulted in 8.8 mg (18%) of 3-(3,5-difluoro-4-((3-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)isothiazol-4-yl)methoxy)phenyl)propanoic acid as a white solid

Sources & evidence

ORD record
ord-d9241b2a0005405e8eb2b23adcb38ec7
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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