Hydrochloric Acid → HCID 59529472, compound

HRID 1877274Notes

Reaction equation

HRID 1877274 reaction equation
[CH:1]1([CH:7]([NH:24][C:25]2[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][CH:26]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[S:10][C:9]=2[CH3:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[NH2:35][CH2:36][CH:37]([OH:42])[C:38]([O:40]C)=[O:39].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[OH-].[Na+]>CN(C)C=O.C(OCC)(=O)C.C(O)C.O1CCCC1.C(N(CC)CC)C>[CH:1]1([CH:7]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:29]([NH:35][CH2:36][CH:37]([OH:42])[C:38]([OH:40])=[O:39])=[O:30])=[CH:32][CH:33]=2)[C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][CH:14]=3)[S:10][C:9]=2[CH3:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68515485HCID 68515485, compoundHCID 71757671Methyl 3-amino-2-hydroxypropanoate hydrochloride

Product 1

HCID 59529472HCID 59529472, compoundYield 53.5%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 4-[(cyclohexyl{2-methyl-5-[4-(trifluoromethyl)phenyl]thiophen-3-yl}methyl)amino]benzoic acid (300 mg) synthesized in Example 280 (4), methyl 3-amino-2-hydroxypropanoate hydrochloride (118 mg), 1-hydroxybenzotriazole monohydrate (117 mg) and triethylamine (106 μL) in N,N-dimethylformamide (10 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (146 mg), and the mixture was stirred at 50° C. for 1 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (70% ethyl acetate/hexane) to give colorless oil. To a mixture of the obtained oil, tetrahydrofuran (5 mL) and ethanol (5 mL) was added 1N aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at room temperature overnight, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), 1N hydrochloric acid (1 mL) was added at 0° C., and the resulting precipitate was collected by filtration to give a white solid. The obtained solid was dissolved in ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure to give the title compound (190 mg, 53%) as a white solid.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (70% ethyl acetate/hexane)
  8. customto give colorless oil
  9. stirringthe mixture was stirred at room temperature overnight
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved in water (10 mL)
  12. addition1N hydrochloric acid (1 mL) was added at 0° C.
  13. filtrationthe resulting precipitate was collected by filtration
  14. customto give a white solid
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-27a45a0939c049b48a6513f231165e2e
Source dataset
uspto-grants-2012_11
Patent number
US08309580B2

Reaction notes

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