Triethylamine → 2-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamide

HRID 1446700Notes

Reaction equation

HRID 1446700 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([F:12])[CH:3]=1.Cl.CN(C)CCCN=C=NCC.[NH2:25][C:26]1[CH:27]=[C:28]([C:36]([N:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)=[O:37])[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1.CCN(CC)CC>C1COCC1.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:25][C:26]2[CH:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[C:28]([C:36]([N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[O:37])[CH:27]=2)=[O:11])=[C:4]([F:12])[CH:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acidHCID 66876746Morpholine, 4-[3-amino-5-(trifluoromethyl)benzoyl]-

Product 1

HCID 685434652-(4-Bromo-2-fluoro-phenyl)-N-[3-(morpholine-4-carbonyl)-5-trifluoromethyl-phenyl]-acetamideYield 15%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve (4-bromo-2-fluoro-phenyl)-acetic acid (692 mg, 3.0 mmol) in THF (24 mL) and add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (618 mg, 3.2 mmol), stir for 10 minutes. Dissolve (3-amino-5-trifluoromethyl-phenyl)-morpholin-4-yl-methanone (740 mg, excluding excess ammonium chloride) from previous step in DCM (24 mL) with Et3N (3.3 mL, 23 mmol). Add the activated acid to the amine mixture and stir at room temperature for overnight. Dilute the resulting suspension with EtOAc and wash with saturated NaHCO3 and aqueous saturated sodium chloride successively. Dry the organic layer (MgSO4), concentrate and purify by silica gel column chromatography (EtOAc/Hexane gradient) to obtain the title compound (15% yield). LCMS (ES), m/z 491 (M+1).

Workup

  1. stirringstir at room temperature for overnight
  2. washwash with saturated NaHCO3 and aqueous saturated sodium chloride successively
  3. dry with materialDry the organic layer (MgSO4)
  4. concentrationconcentrate
  5. custompurify by silica gel column chromatography (EtOAc/Hexane gradient)

Sources & evidence

ORD record
ord-c5e2c30bf045471c93be85cef0b8f2b5
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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