Tetrahydrofuran → HCID 21193257, compound

HRID 1068435Notes

Reaction equation

HRID 1068435 reaction equation
Cl.[F:2][C:3]([F:21])([F:20])[O:4][C:5]1[CH:6]=[C:7]([CH:17]=[CH:18][CH:19]=1)[CH2:8][C:9]1(O)[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]1.[C:22]([C:24]1[CH:37]=[CH:36][C:27]([CH2:28][N:29]2[C:33](C=O)=[CH:32][N:31]=[CH:30]2)=[CH:26][CH:25]=1)#[N:23].C(N(C(C)C)CC)(C)C.S([O-])([O-])(=O)=O.[Mg+2].C([BH3-])#N.[Na+].C1C[O:60][CH2:59]C1>C(Cl)(Cl)Cl.C(O)(=O)C.CO>[OH:60][CH2:59][C:9]1([CH2:8][C:7]2[CH:17]=[CH:18][CH:19]=[C:5]([O:4][C:3]([F:21])([F:20])[F:2])[CH:6]=2)[CH2:14][CH2:13][N:12]([CH2:15][C:33]2[N:29]([CH2:28][C:27]3[CH:36]=[CH:37][C:24]([C:22]#[N:23])=[CH:25][CH:26]=3)[CH:30]=[N:31][CH:32]=2)[CH2:11][CH2:10]1

Participants

10

Reactant 6

HCID 8028TetrahydrofuranHCID 24083Sulfuric acid magnesium salt (1:1)HCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 106322894-[(5-Formylimidazol-1-yl)methyl]benzonitrileHCID 21193430HCID 21193430, compound

Product 1

HCID 21193257HCID 21193257, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of 4-(3-trifluoromethoxybenzyl)-4-hydroxy-methylpiperidine hydrochloride salt (0.62 g, 2.0 mmol), 1-(4-cyano-benzyl)imidazole-5-carboxyaldehyde (0.45 g, 2.0 mmol; Example 1, Step E), diisopropylethylamine (0.53 mL, 3.04 mmol), anhydrous magnesium sulfate (650 mg), activated molecular sieves 3 A powder (750 mg), and anhydrous methanol (6 mL) was stirred at room temp. overnight. The pH of the mixture was adjusted to ˜5 with addition of glacial acetic acid. To the mixture, a solution of sodium cyanoborohydride in THF (2.2 mL, 1 M, 2.2 mmol) was added slowly over a period of 8 h with a syringe pump, and stirred at room temp. overnight. The product mixture was diluted with chloroform, filtered through Celite. The filtrate was washed with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 5-10% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided the title compound as white solid.

Workup

  1. stirringstirred at room temp. overnight
  2. filtrationfiltered through Celite
  3. washThe filtrate was washed with aqueous sodium bicarbonate, brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-0b2bf001d6c24d40a15e650a087182b5
Source dataset
uspto-grants-2001_06
Patent number
US06248756B1

Reaction notes

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