Sodium Hydroxide → HCID 21480643, compound

HRID 1490197Notes

Reaction equation

HRID 1490197 reaction equation
[CH:1]([C:3]12[CH2:17][CH:10]([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=31)[C:9]1[C:4]2=[CH:5][CH:6]=[CH:7][CH:8]=1)=O.[C:18]1([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH:5]1[C:4]2[C:3]3([CH2:1][N:27]4[CH2:26][CH2:25][CH:24]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[CH2:29][CH2:28]4)[CH2:17][CH:10]([C:11]4[C:16]3=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:9]=2[CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 698734-PhenylpiperidineHCID 5003444Sodium cyanoborohydrideHCID 124041419,10-Dihydro-9,10-methanoanthracene-9-carboxaldehyde

Product 1

HCID 21480643HCID 21480643, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a methanol solution (80 mL) of 9-formyl-9,10-dihydro-9,10-methanoanthracene (described in example 5a) (5.00 g, 22.7 mmol) was added a large excess of freshly activated 3 A molecular sieves (approx. 10 g) under an atmosphere of nitrogen. 4-Phenylpiperidine (4.57 g, 28 mmol, 1.25 eq) was added followed by four portions of sodium cyanoborohydride (1.43 g, 22.7 mmol) over 1.3 h. The resulting suspension of sieves and reagents was stirred for 3 days at room temperature. The reaction was treated with 2.5N NaOH (100 mL) and the aqueous phase was extracted with ethyl acetate (1×400 mL). The organic phase was washed with water (3×100 mL), dried over anhydrous sodium sulfate, filtered and reduced to an oil. The reaction product was purified by flash chromatography over silica gel (300 mL, eluent: 50% methylene chloride in hexane) to recover 1.20 g (15%) of the title compound. TLC analysis (Rf 0.19, 50% methylene chloride in hexane). 1H NMR (CDCl3, 300 MHz) 7.22 (m, 9H), 6.93 (m, 4H), 4.27 (s, 1H), 3.43 (s, 2H), 3.13 (m, 2H), 2.62 (d, J=1.4 Hz, 2H), 2.51 (m, 1H), 2.34 (m, 2H), 1.76 (m, 4H) MS (CI, CH4) m/z 366 (M+1,100), 394 (M+29,16) The free base was dissolved in the minimum of methanol and chloroform, acidified with ethereal HCl and the resulting hydrochloride salt precipitated with ether dilution. The solid was filtered, rinsed with fresh ether, and dried in vacuo (50° C., 10 pascal, 18 h) to yield a solid, mp>300° C.

Workup

  1. additionThe resulting suspension of sieves and reagents
  2. extractionthe aqueous phase was extracted with ethyl acetate (1×400 mL)
  3. washThe organic phase was washed with water (3×100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customThe reaction product was purified by flash chromatography over silica gel (300 mL, eluent: 50% methylene chloride in hexane)
  7. customto recover 1.20 g (15%) of the title compound
  8. dissolution1H NMR (CDCl3, 300 MHz) 7.22 (m, 9H), 6.93 (m, 4H), 4.27 (s, 1H), 3.43 (s, 2H), 3.13 (m, 2H), 2.62 (d, J=1.4 Hz, 2H), 2.51 (m, 1H), 2.34 (m, 2H), 1.76 (m, 4H) MS (CI, CH4) m/z 366 (M+1,100), 394 (M+29,16) The free base was dissolved in the minimum of methanol and chloroform
  9. customthe resulting hydrochloride salt precipitated with ether dilution
  10. filtrationThe solid was filtered
  11. washrinsed with fresh ether
  12. customdried in vacuo (50° C., 10 pascal, 18 h)
  13. customto yield a solid, mp>300° C.

Sources & evidence

ORD record
ord-abdf865c5f5e4894945ba20eaed1613b
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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