Acetic Acid → HCID 66701315, compound

HRID 876280Notes

Reaction equation

HRID 876280 reaction equation
C([BH3-])#N.[Na+].[CH2:5]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:18][N:17]([C:19]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[O:20])[CH2:16][CH:15]([C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28])[CH2:14]2)=[CH:9][CH:8]=1)[CH3:6].C(O[C:39]1(O[Si](C)(C)C)[CH2:41][CH2:40]1)C.C(O)(=O)C>O1CCCC1.CO>[CH:39]1([N:24]2[CH2:25][CH2:26][N:21]([C:19]([N:17]3[CH2:18][CH:13]([C:10]4[CH:11]=[CH:12][C:7]([CH2:5][CH3:6])=[CH:8][CH:9]=4)[CH2:14][CH:15]([C:27]([NH:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:28])[CH2:16]3)=[O:20])[CH2:22][CH2:23]2)[CH2:41][CH2:40]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 66701470HCID 66701470, compound

Product 1

HCID 66701315HCID 66701315, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

At RT, 898 μl of a 1-molar solution of sodium cyanoborohydride in tetrahydrofuran were added to a solution of 94 mg (0.20 mmol) of 5-(4-ethylphenyl)-N-phenyl-1-(piperazin-1-ylcarbonyl)piperidine-3-carboxamide, 241 μl (1.20 mmol, 6 eq.) of [(1-ethoxycyclopropyl)oxy](trimethyl)silane, 35 μl (0.62 mmol, 3.1 eq.) of acetic acid and 115 mg of molecular sieves (4 {acute over (Å)}) in 1 ml of methanol. The reaction mixture was stirred under reflux for 5 h and then filtered and adjusted to pH 8 using a 0.2-molar sodium hydroxide solution. After addition of water/dichloromethane and phase separation, the aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 60 mg (65% of theory)

Workup

  1. temperatureunder reflux for 5 h
  2. filtrationfiltered
  3. additionAfter addition of water/dichloromethane and phase separation
  4. extractionthe aqueous phase was extracted twice with dichloromethane
  5. dry with materialThe combined organic phases were dried (sodium sulphate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient)

Sources & evidence

ORD record
ord-fe2274afa15545bd91e83be8287b2ad9
Source dataset
uspto-grants-2015_03
Patent number
US08987248B2

Reaction notes

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