HCID 46175559, compound → HCID 46175555, compound

HRID 1513362Notes

Reaction equation

HRID 1513362 reaction equation
[ClH:1].[F:2][C:3]([F:22])([F:21])[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:9]=1)=[O:5]>[Pt].CO>[ClH:1].[F:21][C:3]([F:2])([F:22])[C:4]([NH:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH:9]=1)=[O:5]

Participants

4

Reactant 1

HCID 46175559HCID 46175559, compound

Product 1

HCID 46175555HCID 46175555, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 887MethanolSolvent

Procedure

A Parr flask is charged with compound 13 (123 g, 0.37 mol) and MeOH (740 mL) at rt, then 5% Pt/C (36.9 g, 30 w/w%) is added. The reaction flask is placed in a Parr hydrogenation system and charged with H2 at 50-60 psi. The mixture is shaken for >48 h while charging H2 until the pressure reached a steady state (H2 was refilled to 50-60 psi every 2-3 hours during day time while 10-20 psi is observed without any further refill after overnight). When HPLC analysis shows completion of the reaction, the reaction mixture is filtered through a pad of Celite. The filtrate is distilled at 40-50° C. while adding n-BuOAc (1.25 L). After completion of distillation of MeOH, additional n-BuOAc (1 L) is added. The resultant suspension is allowed to cool to rt overnight. The suspension is cooled to 10° C., filtered, and dried in oven at 50° C. to give 112 g (89%) of compound 14 as white solid: mp=134° C. Anal. Calcd for C14H10F4N2O—HCl: C, 50.24; H, 3.31; N, 8.37. Found: C, 50.16; H, 3.08; N, 8.38. MS (ESI) m/z 305.4 (M+H). 1H NMR (300 MHz, D2O) δ 7.16-6.98 (m, 3H), 4.34 (s, 2H), 3.42 (d, J=12.9 Hz, 2H), 3.14-2.99 (m, 3H), 1.98-1.81 (m, 4H).

Workup

  1. additioncharged with H2 at 50-60 psi
  2. additionwas refilled to 50-60 psi every 2-3 hours during day time while 10-20 psi
  3. customcompletion of the reaction
  4. filtrationthe reaction mixture is filtered through a pad of Celite
  5. distillationThe filtrate is distilled at 40-50° C.
  6. additionwhile adding n-BuOAc (1.25 L)
  7. distillationAfter completion of distillation of MeOH, additional n-BuOAc (1 L)
  8. additionis added
  9. temperatureThe suspension is cooled to 10° C.
  10. filtrationfiltered
  11. customdried in oven at 50° C.

Sources & evidence

ORD record
ord-4abf6f1995454ec5841542eaf6176193
Source dataset
uspto-grants-2012_07
Patent number
US08217178B2

Reaction notes

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