Cyclohexanone → HCID 58997656, compound

HRID 1592369Notes

Reaction equation

HRID 1592369 reaction equation
[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]([CH3:23])[C@@H:9]([OH:22])[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)([CH3:4])([CH3:3])[CH3:2].[C:25]1(=O)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:24])[NH:7][C@H:8]([CH3:23])[C@@H:9]([OH:22])[CH2:10][N:11]([CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)[CH2:12][CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 5003444Sodium cyanoborohydrideHCID 58997641HCID 58997641, compound

Product 1

HCID 58997656HCID 58997656, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The material from step d (623 mg, 1.83 mMol) and cyclohexanone (179 mg, 1.83 mMol) were dissolved in methanol (5 ml), 4 A molecular sieves were added, and the mixture was stirred at room temperature for 2 hours. To this mixture, sodium cyanoborohydride (173 mg, 2.75 mMol) was added, and the mixture was stirred overnight. Analysis of the reaction mixture by ESI MS showed an M+H which was two AMU higher than that of the desired product, indicating that the imine or aminal hadn't been reduced by sodium cyanoborohydride. The reaction mixture was filtered, the solids were rinsed with EtOAc, and the combined filtrates were concentrated in-vacuo. The residue was dissolved in EtOAc (30 ml), washed with water (2×10 ml), dried over sodium sulfate, and concentrated in-vacuo. The residue was dissolved in methylene chloride (5 ml), sodium triacetoxyborohydride (583 mg, 2.75 mMol) followed by two drops of glacial acetic acid were added, and the mixture was stirred at room temperature for three days. The reaction was worked up by diluting with water (50 ml), adjusting the pH of the mixture to >10 with 1N NaOH, and extracting with EtOAc (3×30 ml). The combined organic phases were dried over sodium sulfate, and concentrated to a yellow oil. This oil was purified via flash chromatography, eluting with EtOAc to yield 310 mg of a colorless oil as product. ESI+MS detects 423 (M+H).

Workup

  1. addition4 A molecular sieves were added
  2. stirringthe mixture was stirred overnight

Sources & evidence

ORD record
ord-36eb8e1e7bae4e6ea704215d85785d13
Source dataset
uspto-grants-2007_11
Patent number
US07291744B2

Reaction notes

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