3-(Trifluoromethyl)benzeneacetic acid → HCID 67409812, compound

HRID 714674Notes

Reaction equation

HRID 714674 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[F:34][C:35]([F:47])([F:46])[C:36]1[CH:37]=[C:38]([CH2:42][C:43]([OH:45])=O)[CH:39]=[CH:40][CH:41]=1.C(N(CC)C(C)C)(C)C.[Cl:57][C:58]1[S:62][C:61]([C:63]2[N:67]([CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=3[F:75])[C:66](=[O:76])[N:65]([CH2:77]/[C:78](=[N:80]/O)/[NH2:79])[N:64]=2)=[CH:60][CH:59]=1>CN(C=O)C.O>[Cl:57][C:58]1[S:62][C:61]([C:63]2[N:67]([CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=3[F:75])[C:66](=[O:76])[N:65]([CH2:77][C:78]3[N:80]=[C:43]([CH2:42][C:38]4[CH:39]=[CH:40][CH:41]=[C:36]([C:35]([F:34])([F:47])[F:46])[CH:37]=4)[O:45][N:79]=3)[N:64]=2)=[CH:60][CH:59]=1

Participants

7

Reactant 4

HCID 676953-(Trifluoromethyl)benzeneacetic acidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 88064403HCID 88064403, compound

Product 1

HCID 67409812HCID 67409812, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under argon, 81 mg (0.16 mmol) of benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate were added to a solution of 29 mg (0.14 mmol) of 3-(trifluoromethyl)phenylacetic acid and 27 μl (0.16 mmol) of N,N-diisopropylethylamine in 1.3 ml of dry DMF. After 30 min of stirring, 50 mg (0.13 mmol) of the compound from Example 25A were added and the mixture was stirred at RT for 18 h. 2 ml of water were then added, and the mixture was extracted three times with in each case 5 ml of ethyl acetate. The combined organic phases were washed with in each case 5 ml of water and sodium chloride solution, filtered though Extrelut and concentrated under reduced pressure. The residue was dissolved in 2 ml of DMF and stirred in a microwave oven at 250° C. for 15 min. After cooling, the solvent was removed under reduced pressure on a rotary evaporator and the crude product was purified by chromatography [Method 15]. This gave 25 mg (34% of theory) of the target compound as a dark-yellow resin.

Workup

  1. stirringthe mixture was stirred at RT for 18 h
  2. extractionthe mixture was extracted three times with in each case 5 ml of ethyl acetate
  3. washThe combined organic phases were washed with in each case 5 ml of water and sodium chloride solution
  4. filtrationfiltered though Extrelut
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in 2 ml of DMF
  7. stirringstirred in a microwave oven at 250° C. for 15 min
  8. temperatureAfter cooling
  9. customthe solvent was removed under reduced pressure on a rotary evaporator
  10. customthe crude product was purified by chromatography [Method 15]

Sources & evidence

ORD record
ord-c585a96061f3439880336773ac218502
Source dataset
uspto-grants-2015_11
Patent number
US09187466B2

Reaction notes

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