Dimethylformamide → HCID 58617278, compound

HRID 547580Notes

Reaction equation

HRID 547580 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[C:12]([F:15])([F:14])[F:13].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[CH2:27]([S:29]([CH2:32][CH2:33][NH:34][C@@H:35]([C:37]1[N:46]([C:47]2[CH:52]=[CH:51][C:50]([O:53][CH2:54][C:55]([F:58])([F:57])[F:56])=[CH:49][CH:48]=2)[C:45](=[O:59])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]=1)[CH3:36])(=[O:31])=[O:30])[CH3:28].C(N(CC)CC)C>ClCCl>[CH2:27]([S:29]([CH2:32][CH2:33][N:34]([C@@H:35]([C:37]1[N:46]([C:47]2[CH:48]=[CH:49][C:50]([O:53][CH2:54][C:55]([F:58])([F:57])[F:56])=[CH:51][CH:52]=2)[C:45](=[O:59])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]=1)[CH3:36])[C:9](=[O:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:12]([F:15])([F:14])[F:13])[CH:4]=1)(=[O:30])=[O:31])[CH3:28]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27375934-Fluoro-3-(trifluoromethyl)phenylacetic acidHCID 58617279HCID 58617279, compound

Product 1

HCID 58617278HCID 58617278, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Fluoro-3-trifluoromethylphenylacetic acid (164 mg, 0.74 mmol) was dissolved in dichloromethane and cooled to 0° C. Oxalyl chloride (64 μL, 0.74 mmol) was added, then after 5 min., N,N-dimethylformamide (5.7 μL, 0.07 mmol) was added. The reaction stirred at 0° C. for 30 min. and room temperature for 1 h. The solution was added slowly to a mixture of 12 (210 mg, 0.43 mmol) and triethylamine (182 μL, 1.30 mmol) in dichloromethane at −78° C. This stirred for 30 min., then was washed with saturated aqueous sodium bicarbonate and brine. It was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purified by reverse-phase HPLC to yield 256 mg of a colorless solid, 11. MS (ESI+): m/z=715.2 [M+H]+. 1H NMR (500 MHz; CDCl3; T=298 K): δ 9.10-8.95 (m, 1H), 8.66-8.58 (m, 1H), 7.78-7.57 (m, 1H), 7.47-7.36 (m, 3H), 7.24 (m, 1H), 7.13 (m, 3H), 5.03 (q, 1H, J=7.4 Hz), 4.43 (quint, 2H, J=8.0 Hz), 3.77 (s, 1H), 3.71 (m, 1H), 3.62-3.49 (m, 2H), 3.23-3.09 (m, 3H), 2.81 (d, 1H, J=12.9 Hz), 2.62-2.41 (m, 1H), 2.14-1.90 (m, 2H), 1.68 (broad s, 2H), 1.64-1.45 (m, 3H) ppm.

Workup

  1. stirringThis stirred for 30 min.
  2. washwas washed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialIt was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurified by reverse-phase HPLC

Sources & evidence

ORD record
ord-7a5699739f084d268f3bf5a3d3c0c25a
Source dataset
uspto-grants-2011_05
Patent number
US07939538B2

Reaction notes

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