Acetic Acid → HCID 19698704, compound

HRID 1609113Notes

Reaction equation

HRID 1609113 reaction equation
[CH:1]1[C:14]2[C:13]3([CH:16]=O)[CH2:15][CH:6]([C:7]4[C:12]3=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH:18]1[CH2:28][CH2:27][CH:21](C(OCC)=O)[CH2:20][CH2:19]1.[C:29]([OH:32])(=O)[CH3:30].[C:33]([BH3-])#N.[Na+]>CO>[CH:11]1[C:12]2[C:13]3([CH2:16][N:18]4[CH2:28][CH2:27][CH:21]([C:29]([OH:32])([CH3:30])[CH3:33])[CH2:20][CH2:19]4)[CH2:15][CH:6]([C:5]4[C:14]3=[CH:1][CH:2]=[CH:3][CH:4]=4)[C:7]=2[CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 5003444Sodium cyanoborohydride2×HCID 124041419,10-Dihydro-9,10-methanoanthracene-9-carboxaldehyde

Product 1

HCID 19698704HCID 19698704, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 9,10-dihydro-9,10-methanoanthracene-9-carboxaldehyde (1.00 g, 4.54 mmol) and ethyl isonipecotate (1.07 g, 6.81 mmol) in methanol was treated with glacial acetic acid until the solution had a pH~5. Crushed 3 angstrom sieves (1.0 g) were added, and the mixture was stirred at room temperature for 2 h. Sodium cyanoborohydride (630 mg, 10.03 mmol) was then added, and the mixture was stirred at room temperature for 18 h. After this time, additional quantities of sodium cyanoborohydride (100 mg) and 3 angstrom sieves (1.0 g, crushed) were added, and the mixture was stirred an additional 6 h. The solids were removed by filtration and washed with chloroform (3×25 mL). The filtrate was washed sequentially with 10% aqueous sodium hydroxide (2×30 mL) and brine (30 mL). The aqueous washes were extracted with chloroform (2×50 mL). The organic extracts were combined, dried over potassium carbonate, filtered and evaporated to leave a dark semi-solid mass (1.4 g). Purification by flash chromatography over silica gel (eluant: 99.5:0.5 chloroform/methanol) afforded the title compound as a light yellow solid (800 mg, 2.21 mmol, 49%).

Workup

  1. customCrushed 3 angstrom
  2. additionwere added
  3. stirringthe mixture was stirred at room temperature for 18 h
  4. additionwere added
  5. stirringthe mixture was stirred an additional 6 h
  6. customThe solids were removed by filtration
  7. washwashed with chloroform (3×25 mL)
  8. washThe filtrate was washed sequentially with 10% aqueous sodium hydroxide (2×30 mL) and brine (30 mL)
  9. extractionThe aqueous washes were extracted with chloroform (2×50 mL)
  10. dry with materialdried over potassium carbonate
  11. filtrationfiltered
  12. customevaporated
  13. customto leave a dark semi-solid mass (1.4 g)
  14. customPurification by flash chromatography over silica gel (eluant: 99.5:0.5 chloroform/methanol)

Sources & evidence

ORD record
ord-0c7e65f2c86e429e89ca4b2f12f083fc
Source dataset
uspto-grants-1995_03
Patent number
US05399568

Reaction notes

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