Sulfuric Acid → HCID 21480623, compound

HRID 1490220Notes

Reaction equation

HRID 1490220 reaction equation
[CH:1]1[C:14]2[C:13]3([CH2:16][N:17]4[CH2:22][CH2:21][C:20]([C:24]5[CH:25]=[N:26][CH:27]=[C:28]([C:30]67OCC(C)(C[O:35]6)[CH2:32][O:31]7)[CH:29]=5)([OH:23])[CH2:19][CH2:18]4)[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.S(=O)(=O)(O)O.[OH-].[Na+]>CO>[CH:11]1[C:12]2[C:13]3([CH2:16][N:17]4[CH2:22][CH2:21][C:20]([C:24]5[CH:25]=[N:26][CH:27]=[C:28]([C:30]([O:31][CH3:32])=[O:35])[CH:29]=5)([OH:23])[CH2:19][CH2:18]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

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 21480662HCID 21480662, compound

Product 1

HCID 21480623HCID 21480623, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a heterogeneous solution of 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(5-(4-methyl-2,6,7-trioxabicyclo[2.2.2]oct-1-yl)-3-pyridyl)piperidin-4-ol (0.970 g, 1.90 mmol) in methanol (5 mL) under nitrogen was added sulfuric acid (0.21 mL, 2 eq). The suspension dissolved as the acid was added. The reaction was stirred for 24 h and basified with 2.5N NaOH (25 mL). The aqueous phase was extracted with ethyl acetate (3×20 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to an oil. The reaction product was purified by flash chromatography over silica gel (65 mL, eluent: 20% hexane in ethyl acetate) to yield 0.560 g (67%) of the title compound as a white solid. TLC analysis (Rf 0.21, 20% hexane in ethyl acetate). 1H NMR (CDCl3, 300 MHz) 9.10 (d, J=1.8 Hz, 1H), 8.93 (d, J=2.3 Hz, 1H), 8.38 (t, J=2.1Hz, 1H), 7.27 (m, 2H), 7.18 (m, 2H), 6.95 (m, 4H), 4.29 (br s, 1H), 3.95 (s, 3H), 3.49 (s, 2H), 2.95 (m, 2H), 2.73 (m, 2H), 2.63 (s, 2H), 2.15 (m, 2H), 1.76 (m, 2H) MS (CI, CH4) m/z 441 (M+1,100), 469 (M+29,15), 423 (11), 145 (9), 103 (11), 85 (20) The free base was dissolved in ether containing methylene chloride and acidified with ethereal HCl. The hydrochloride salt was precipitated with ether dilution, filtered, rinsed with fresh ether and dried in vacuo (60° C., 10 pascal, 18 h) to yield a white solid, mp 243°-247° C. (dec).

Workup

  1. dissolutionThe suspension dissolved as the acid
  2. additionwas added
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×20 mL)
  4. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customThe reaction product was purified by flash chromatography over silica gel (65 mL, eluent: 20% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-2ffe5da1c3f741f582c5bb2390922c60
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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