Acetic Acid → HCID 58997344, compound

HRID 1591858Notes

Reaction equation

HRID 1591858 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C=O.[C:25](O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N:14]([CH3:25])[CH:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 58997377HCID 58997377, compound

Product 1

HCID 58997344HCID 58997344, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine (3-(1-methylpiperidin-4-ylamino)phenyl)carbamic acid tert-butyl ester (Preparation 9, 1.15 g, 3.77 mmol), methanol (15 mL) and formaldehyde (37% aq., 0.92 mL, 11.3 mmol). Stir at room temperature for 45 min. Cool to 0° C. Add acetic acid (0.22 mL, 3.77 mmol) and sodium cyanoborohydride (414 mg, 6.59 mmol). Stir at room temperature overnight. Concentrate to dryness. Dissolve the residue in a 2/1 mixture of ethyl acetate and hexanes (20 mL) and wash with sodium hydroxide (1N aq., 2×20 mL). Separate the organic layer and dry over magnesium sulfate. Filter and concentrate under reduced pressure. Purify through flash chromatography eluting with a 20/1 mixture of dichloromethane and 2M ammonia in methanol to provide the title compound (990 mg, 82%): mass spectrum (ion spray): m/z=320.3 (M+1).

Workup

  1. temperatureCool to 0° C
  2. stirringStir at room temperature overnight
  3. concentrationConcentrate to dryness
  4. dissolutionDissolve the residue
  5. additionin a 2/1 mixture of ethyl acetate and hexanes (20 mL)
  6. washwash with sodium hydroxide (1N aq., 2×20 mL)
  7. customSeparate the organic layer
  8. dry with materialdry over magnesium sulfate
  9. filtrationFilter
  10. concentrationconcentrate under reduced pressure
  11. customPurify through flash chromatography
  12. washeluting with a 20/1 mixture of dichloromethane and 2M ammonia in methanol

Sources & evidence

ORD record
ord-3825ded44fd5455cabfd820750d36191
Source dataset
uspto-grants-2007_11
Patent number
US07291632B2

Reaction notes

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