1,2-Dichloroethane → HCID 58617304, compound

HRID 547577Notes

Reaction equation

HRID 547577 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]2[C@H:21]([NH:23][CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]2)[CH3:22])=[CH:6][CH:5]=1)[CH3:2].[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42](O)=[O:43])=[CH:37][C:36]=1[C:45]([F:48])([F:47])[F:46].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(Cl)CCl>CN(C)C=O.ClCCl>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]2[C@H:21]([N:23]([CH2:24][CH:25]2[CH2:30][CH2:29][N:28]([CH:31]([CH3:32])[CH3:33])[CH2:27][CH2:26]2)[C:42](=[O:43])[CH2:41][C:38]2[CH:39]=[CH:40][C:35]([F:34])=[C:36]([C:45]([F:46])([F:48])[F:47])[CH:37]=2)[CH3:22])=[CH:8][CH:9]=1)[CH3:2]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-Methylmorpholine2×HCID 757711-Hydroxybenzotriazole2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27375934-Fluoro-3-(trifluoromethyl)phenylacetic acidHCID 58617287HCID 58617287, compound

Product 1

HCID 58617304HCID 58617304, compoundYield 57.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 49.3 g A2 (0.11 mol, 1.00 equiv.) and 29.3 g 4-fluoro-3-(trifluoromethyl)phenylacetic acid (0.13 mol, 1.20 equiv.) in 120 mL N,N-dimethylformamide, DMF, and 40 mL dichloromethane at room temperature was added 12 mL N-methylmorpholine, NMM (0.11 mol, 1.00 equiv.) and 14.9 g 1-hydroxybenzotriazole, HOBT (0.11 mol, 1.00 equiv.). To the solution was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, EDC (0.22 mol, 2.00 equiv.) in two equivalent portions at a 5 min. interval. The reaction mixture was stirred at room temperature for 16 h then taken-up in 800 mL ethyl acetate and washed with saturated aqueous sodium bicarbonate and aqueous brine six times. The organic extract was dried over magnesium sulfate, filtered and concentrated in vacuo to afford a glassy solid. The product was purified by recrystallization from diethyl ether to yield 41 g of 1 as a colorless solid. 1H NMR (400 MHz; d6-DMSO; T=393 K): δ 0.92 (d, J=6.6 Hz, 6H), 0.95-1.20 (m, 2H), 1.35 (t, J=7.0 Hz, 3H), 1.32-1.50 (m, 2H), 1.50 (d, J=6.6 Hz, 3H), 1.58 (d, J=1.0 Hz, 1H), 1.85 (dd, J=10.3, 10.3 Hz, 1H), 1.99 (dd, J=11.4, 11.4 Hz, 1H), 2.52-2.68 (m, 2H), 2.75 (d, J=11.4 Hz, 1H), 2.88 (br s, 1H), 3.10 (dd, J=9.1, 14.8 Hz, 1H), 3.30 (dd, J=9.1, 13.7 Hz, 1H), 3.52 (br s, 1H), 4.09 (qt, J=7.0 Hz, 2H), 5.12 (qt, J=9.12 Hz, 1H), 7.00-7.13 (m, 2H), 7.18 (d, J=10.3 Hz, 1H), 7.30 (dd, J=10.3, 10.3 Hz, 1H), 7.33-7.48 (m, 3H), 7.57 (dd, J=9.5, 9.5 Hz, 1H), 7.72 (d, J=9.5 Hz, 1H), 7.87 (dd, J=9.5, 9.5 Hz, 1H), 8.15 (d, J=7.8 Hz, 1H) ppm; MS (ESI+) m/z=653.3 [M+H]+; Analytical calculated: 66.24%, C, 6.18% H, 11.64% F and 8.58% N. Found: 66.17% C, 6.05% H, 8.56% N, 11.59% F.

Workup

  1. washtaken-up in 800 mL ethyl acetate and washed with saturated aqueous sodium bicarbonate and aqueous brine six times
  2. extractionThe organic extract
  3. dry with materialwas dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a glassy solid
  7. customThe product was purified by recrystallization from diethyl ether

Sources & evidence

ORD record
ord-4d932c969e794d418651304c4bebf83d
Source dataset
uspto-grants-2011_05
Patent number
US07939538B2

Reaction notes

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