Trifluoroacetic acid → HCID 87182467, compound

HRID 254795Notes

Reaction equation

HRID 254795 reaction equation
[NH2:1][C@@H:2]1[C@@H:8]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C@H:7]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[C@@H:6]([CH2:29][O:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[O:5][CH:3]1[OH:4].C(N(C(C)C)CC)(C)C.[F:49][C:50]([F:55])([F:54])[C:51](O)=[O:52].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][O:9][C@H:8]2[C@H:7]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[C@@H:6]([CH2:29][O:30][CH2:31][C:32]3[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=3)[O:5][CH:3]([OH:4])[C@@H:2]2[NH:1][C:51](=[O:52])[C:50]([F:55])([F:54])[F:49])=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 66862433HCID 66862433, compound

Product 1

HCID 87182467HCID 87182467, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of the amine 64 (75.6 mmol) in dry chloroform (400 ml) at 0° C. was added diisoproplyethylamine (113.4 mmol) and trifluoroacetic acid (16.0 mL, 113.4 mmol). The resulting reaction mixture was then stirred for 30 min after which time the reaction was allowed to return to room temperature and stir for a further 1 h. At this time the reaction was cooled to 0° C. and further diisoproplyethylamine (113.4 mmol) and trifluoroacetic acid (113.4 mmol) added, the reaction was allowed to return to room temperature and stirred for 3 h. The reaction mixture was then poured into dilute sodium hydrogen carbonate and the mixture stirred for 30 min. The solid was washed with water, transferred to a flask and dried by co-evaporation with acetonitrile to give the crude product. Ethyl acetate was then added to the residue and the resulting suspension refluxed for 2 h. Petrol ether (˜300 mL) was then added to this, the mixture cooled to room temperature, and the resulting solid filtered and dried under high vacuum to give the desired product 65 as a solid (77%), δH (400 MHz; CDCl3) 3.04-3.17 (1 H, m), 3.54-3.60 (2 H, m), 3.61-3.71 (2 H, m), 3.79 (3 H, s), 3.80 (3 H, s), 3.81 (3 H, s), 4.01 [dt, J 3.0 Hz and J 10.4 Hz] and 4.16 [dt, J 3.7 Hz and J 10.1 Hz] (1 H), 4.43 (2 H, t, J 10.4 Hz), 4.50-4.60 (2 H, m), 4.66-4.78 (2 H, m), 5.23 (1 H, d, J 4.0 Hz), 6.11 (1 H, br d, J 2.9 Hz), 6.80-6.90 (6 H, m), 7.06 (2 H, d, J 11.1 Hz), 7.18 (2 H, d, J 12.6 Hz) and 7.24 (2 H, d, J 11.1 Hz); LCMS [M+Na]+=658.2.

Workup

  1. customThe resulting reaction mixture
  2. customto return to room temperature
  3. stirringstir for a further 1 h
  4. customto return to room temperature
  5. stirringstirred for 3 h
  6. stirringthe mixture stirred for 30 min
  7. washThe solid was washed with water
  8. customtransferred to a flask
  9. dry with materialdried by co-evaporation with acetonitrile
  10. customto give the crude product
  11. temperaturethe resulting suspension refluxed for 2 h
  12. temperaturecooled to room temperature
  13. filtrationthe resulting solid filtered
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-3b825569333c4570adb2a7196638999f
Source dataset
uspto-grants-2011_01
Patent number
US07875707B2

Reaction notes

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