Diisopropylethylamine → 1204737-09-6

HRID 2355297Notes

Reaction equation

HRID 2355297 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:27]=[CH:26][C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])=[C:12]([OH:21])[C:11]=2[C:22]([F:25])([F:24])[F:23])=[CH:6][CH:5]=1.[CH3:28][N:29]1[CH:33]=[C:32]([C:34](O)=[O:35])[N:31]=[CH:30]1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>O1CCCC1.O>[OH:21][C:12]1[C:11]([C:22]([F:23])([F:24])[F:25])=[C:10]([CH:15]=[CH:14][C:13]=1[C:16](=[O:20])[CH:17]([CH3:19])[CH3:18])[O:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:34]([C:32]2[N:31]=[CH:30][N:29]([CH3:28])[CH:33]=2)=[O:35])=[CH:27][CH:26]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67175712HCID 67175712, compound

Product 1

HCID 445958511204737-09-6Yield 148.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Mechanically stir suspensions of 1-[4-(4-aminomethyl-benzyloxy)-2-hydroxy-3-trifluoromethyl-phenyl]-2-methyl-propan-1-one hydrochloride (244 g, 604 mmol), 1-methyl-imidazole-4-carboxylic acid (95 g, 753 mmol), and 1-hydroxybenzotriazole hydrate (118 g, 770 mmol) in tetrahydrofuran (8 L) in two separate 22-L Morton flasks. Treat each solution with diisopropylethylamine (269 mL, 1.54 mol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (145 g, 756 mmol) in single portions and stir overnight at room temperature. Dilute each with 4 L of water and extract twice with 4 L of ethyl acetate. Wash organic layers with saturated sodium chloride solution, dry with magnesium sulfate, filter, and evaporate the filtrates to tan foams. Combine the foams and recrystallize from isopropanol (6 L) to afford the title compound (426 g, 74% yield). m.p. 164.7° C.; HPLC Rt=4.86 min; 1H NMR (DMSO-d6) δ 13.95 (s, 1H), 8.45 (t, J=8.0 Hz, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.63 (d, J=12.0 Hz, 2H), 7.33 (ABq, J=12.0, 8.0 Hz, 4H), 6.89 (d, J=8.0 Hz, 1H), 5.32 (s, 2H), 4.39 (d, J=8.0 Hz, 2H), 3.71 (hept, J=8.0 Hz, 1H), 3.67 (s, 3H), 1.12 (d, J=8.0 Hz, 6H); 19F NMR (DMSO-d6) δ-54.10; MS (m/z): 476.0 (M+1).

Workup

  1. extractionextract twice with 4 L of ethyl acetate
  2. dry with materialWash organic layers with saturated sodium chloride solution, dry with magnesium sulfate
  3. filtrationfilter
  4. customevaporate the filtrates to tan foams
  5. customCombine the foams and recrystallize from isopropanol (6 L)

Sources & evidence

ORD record
ord-96d1ff10dc25404992341d182439a87d
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

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