Hydrochloric Acid → HCID 68156838, compound

HRID 537518Notes

Reaction equation

HRID 537518 reaction equation
[CH:1]1([CH2:4][CH:5]([C:22]2[CH:31]=[CH:30][C:25]([C:26](OC)=[O:27])=[CH:24][CH:23]=2)[O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.O.[OH-].[Li+].Cl.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1.[NH2:67][CH2:68][CH2:69][C:70]([O:72][CH3:73])=[O:71]>CO.O>[CH:1]1([CH2:4][CH:5]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([NH:67][CH2:68][CH2:69][C:70]([O:72][CH3:73])=[O:71])=[O:27])=[CH:24][CH:23]=2)[O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[CH:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[N:14]3)=[CH:11][CH:12]=2)[CH2:3][CH2:2]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 168937Lithium hydroxide, monohydrateHCID 192794Methyl beta-alanateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68178606HCID 68178606, compound

Product 1

HCID 68156838HCID 68156838, compoundYield 109.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a mixture of (+/−)-methyl 4-(2-cyclopropyl-1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)ethyl)benzoate (104 mg, 0.242 mmol) in methanol (1.2 mL) and water (0.2 L) was added lithium hydroxide monohydrate (50.08 mg, 1.21 mmol) at room temperature. The resulting mixture was stirred overnight. The reaction mixture was poured into water and acidified to pH=6 with 1N hydrochloric acid. The solution was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in N,N-dimethylformamide (0.84 mL) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (95.8 mg, 0.252 mmol) was added, followed by N-methylmorpholine (50.9 mg, 0.504 mmol). The reaction mixture was stirred for 30 minutes at room temperature. Methyl 3-aminopropionate (23.4 mg, 0.168 mmol) was then added and the reaction was stirred for 48 hours. The reaction mixture was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated. Purification by column chromatography gave (+/−)-methyl 3-(4-(2-cyclopropyl-1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenoxy)ethyl)benzamido)propanoate (92 mg, 76%). MS (M+Na): 524.1.

Workup

  1. extractionThe solution was extracted with dichloromethane
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (0.84 mL)
  6. stirringThe reaction mixture was stirred for 30 minutes at room temperature
  7. stirringthe reaction was stirred for 48 hours
  8. customThe reaction mixture was partitioned between brine and ethyl acetate
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. dry with materialThe combined extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by column chromatography

Sources & evidence

ORD record
ord-6182b4a4beb1425cb37f87af068675c8
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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