Acetic Acid → HCID 16754249, compound

HRID 132815Notes

Reaction equation

HRID 132815 reaction equation
[N:1]1([C:7]([C:9]2[N:10]([CH2:26][C:27]([F:30])([F:29])[F:28])[C:11]3[C:16]([CH:17]=2)=[CH:15][C:14]([O:18][CH2:19][CH:20]2[O:25][CH2:24][CH2:23][NH:22][CH2:21]2)=[CH:13][CH:12]=3)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.FC(F)(F)C([O-])=O.O.[CH3:39][C:40]([CH3:42])=O.C(O)(=O)C.C([BH3-])#N.[Na+]>O1CCCC1>[CH:40]([N:22]1[CH2:23][CH2:24][O:25][CH:20]([CH2:19][O:18][C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[N:10]([CH2:26][C:27]([F:30])([F:29])[F:28])[C:9]([C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[O:8])=[CH:17]3)[CH2:21]1)([CH3:42])[CH3:39]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 180AcetoneHCID 962WaterHCID 84468TrifluoroacetateHCID 5003444Sodium cyanoborohydrideHCID 67527009HCID 67527009, compound

Product 1

HCID 16754249HCID 16754249, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a solution of morpholin-4-yl-[5-(morpholin-2-ylmethoxy)-1-(2,2,2-trifluoro-ethyl)-1H-indol-2-yl]-methanone as trifluoroacetate salt (example 1, step 2, 120 mg, 1.0 eq.) in tetrahydrofuran (2 mL) were successively added water (0.004 mL, 1.1 eq.), acetone (0.019 mL, 1.5 eq.), acetic acid (0.040 mL, 3.0 eq.) and a solution of sodium cyanoborohydride in tetrahydrofuran (1M, 0.33 mL, 1.5 eq.). The reaction mixture was stirred at 55° C. overnight and concentrated in vacuo. Water (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue and the solution was washed with ethyl acetate and then basified by addition of an aqueous solution of potassium carbonate. The aqueous fraction was extracted with ethyl acetate and the combined organic layers were washed with brine. The organic residue was purified on silica, eluting with 98:2 dichloromethane/methanol, to yield 45 mg (43%) of the desired product as white foam. MS (m/e): 470.5 (MH+, 100%).

Workup

  1. concentrationconcentrated in vacuo
  2. additionWater (5 mL) and hydrochloric acid (1N, 1.5 mL) were added to the residue
  3. washthe solution was washed with ethyl acetate
  4. additionbasified by addition of an aqueous solution of potassium carbonate
  5. extractionThe aqueous fraction was extracted with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. customThe organic residue was purified on silica
  8. washeluting with 98:2 dichloromethane/methanol

Sources & evidence

ORD record
ord-3ebeae3676fa4aba9336e9001c70eb6a
Source dataset
uspto-grants-2008_06
Patent number
US07388095B2

Reaction notes

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