Ethyl Acetate → HCID 68157773, compound

HRID 1892721Notes

Reaction equation

HRID 1892721 reaction equation
[CH3:1][CH:2]([CH3:30])[CH2:3][CH:4]([C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[N:23]=[CH:22]2)=[CH:17][CH:16]=1)[O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](O)=[O:11])=[CH:8][CH:7]=1.Cl.[CH3:32][NH:33]CCC(O)=O.Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.[C:61]([O:64][CH2:65]C)(=[O:63])[CH3:62]>ClCCl.C(N(CC)CC)C>[CH3:30][CH:2]([CH3:1])[CH2:3][CH:4]([C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[N:23]=[CH:22]2)=[CH:19][CH:20]=1)[O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([NH:33][CH2:32][CH2:62][C:61]([O:64][CH3:65])=[O:63])=[O:11])=[CH:8][CH:7]=1

Participants

8

Reactant 5

HCID 8857Ethyl AcetateHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 45791941N-Methyl-b-alanine HClHCID 68157828HCID 68157828, compound

Product 1

HCID 68157773HCID 68157773, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

4-(3-Methyl-1-(4-(4-(trifluoromethyl)-1H-imidazol-1-yl)phenyl)butoxy)benzoic acid (65 mg, 0.16 mmol), methyl beta-alanine hydrochloride (31 mg, 0.16 mmol), and triethylamine (0.031 mL) were dissolved in dichloromethane (1 mL). 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (34 mg, 0.18 mmol) was added. The solution was stirred at room temperature for 15 minutes, and 1-hydroxy-7-azabenzotriazole (34 mg, 0.25 mmol) was then added. The resulting yellow solution was stirred overnight. After 18 hours, the reaction was diluted with ethyl acetate (20 mL) and washed with water (25 mL) and brine (10 mL). The organics were dried over magnesium sulfate, filtered and concentrated. Purification by column chromatography (0-100% ethyl acetate in heptane) gave (+/−)-methyl 3-(4-(3-methyl-1-(4-(4-(trifluoromethyl)-1H-imidazol-1-yl)phenyl)butoxy)benzamido)propanoate (70 mg, 90%). 1H NMR (400 MHz, CDCl3, δ): 7.84 (s, 1H), 7.67-7.62 (m, 2H), 7.58 (s, 1H), 7.53-7.46 (m, 2H), 7.39-7.34 (m 2H), 6.89-6.84 (m, 2H), 6.72 (t, J=5.9 Hz, 1H), 5.29 (dd, J=8.9, 4.5 Hz, 1H), 3.72-3.65 (m, 5H), 2.63 (m, 2H), 2.03 (m, 1H), 1.95-1.83 (m, 1H), 1.65-1.58 (m, 1H), 1.03 (d, J=6.6 Hz, 3H), 0.99 (d, J=6.3 Hz, 3H). MS (M+1): 504.0.

Workup

  1. stirringThe resulting yellow solution was stirred overnight
  2. waitAfter 18 hours
  3. washwashed with water (25 mL) and brine (10 mL)
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography (0-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-7a51201a970e44f3b2662e17d4c70eb6
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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