Tetrahydrofuran → HCID 10121063, compound

HRID 1359130Notes

Reaction equation

HRID 1359130 reaction equation
[NH2:1][CH2:2][CH:3]([C:10]1([OH:32])[CH2:15][CH2:14][N:13]([C:16]([C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=2)=[O:17])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:33][N:34]1[CH2:39][CH2:38][C:37](=O)[CH2:36][CH2:35]1.[O:41]1CCC[CH2:42]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+].C(N1C=CN=C1)(N1C=CN=C1)=O>O>[F:31][C:28]([F:29])([F:30])[C:20]1[CH:19]=[C:18]([CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=1)[C:16]([N:13]1[CH2:14][CH2:15][C:10]2([O:32][C:42](=[O:41])[N:1]([CH:37]3[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]3)[CH2:2][CH:3]2[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:11][CH2:12]1)=[O:17]

Participants

8

Reactant 6

HCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 740491-Methyl-4-piperidoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 18179607HCID 18179607, compound

Product 1

HCID 10121063HCID 10121063, compoundYield 66.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 460 mg (1 mmol) [4-(2-amino-1-phenyl-ethyl)-4-hydroxy-piperidin-1-yl]-(3,5-bis-trifluoromethyl-phenyl)-methanone and 113 mg (1 mmol) of 1-methyl-4-piperidone in 1 ml of tetrahydrofurane 0.114 ml (2 mmol) acetic acid and 295 mg (1.4 mmol) sodium triacetoxyborohydride were added. The reaction mixture was shaken over night at room temperature. A solution of saturated sodium hydrogencarbonate was added, and the solution was extracted three times with dichloromethane. The combined organic phases were dried and evaporated under pressure. The residue was dissolved in 9 ml of tetrahydrofurane and 462 mg (2.85 mmol) 1,1′-carbonyl-diimidazole was added. The mixture was stirred under argon at room temperature over night and at 60° C. for three days. After cooling, water (5 ml) was added, and the solution was extracted three times with dichloromethane. The combined organic layers were dried and evaporated. The residue was purified by column chromatography (SiO2, dichloromethane/methanol=90:10) to yield 388 mg (66%) of the title compound.

Workup

  1. extractionthe solution was extracted three times with dichloromethane
  2. customThe combined organic phases were dried
  3. customevaporated under pressure
  4. dissolutionThe residue was dissolved in 9 ml of tetrahydrofurane
  5. stirringThe mixture was stirred under argon at room temperature over night and at 60° C. for three days
  6. temperatureAfter cooling
  7. extractionthe solution was extracted three times with dichloromethane
  8. customThe combined organic layers were dried
  9. customevaporated
  10. customThe residue was purified by column chromatography (SiO2, dichloromethane/methanol=90:10)

Sources & evidence

ORD record
ord-bd7720dbed8145d39518a98805fa972c
Source dataset
uspto-grants-2003_07
Patent number
US06599900B2

Reaction notes

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