Sodium Hydroxide → HCID 21480643, compound

HRID 1721774Notes

Reaction equation

HRID 1721774 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. dissolutionThe 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-d9a2a9f6f5d0496abcc3ab646b1621bf
Source dataset
uspto-grants-1996_04
Patent number
US05512575

Reaction notes

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