Tetrahydrofuran → HCID 21480671, compound

HRID 1490214Notes

Reaction equation

HRID 1490214 reaction equation
O1CCCC1.[Si]([O:13][CH2:14][C:15]1[CH:16]=[C:17]([C:21]2([OH:44])[CH2:26][CH2:25][N:24]([CH2:27][C:28]34[CH2:43][CH:35]([C:36]5[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][C:41]=53)[C:34]3[C:29]4=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:23][CH2:22]2)[CH:18]=[N:19][CH:20]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O>[Cl:42][C:39]1[CH:38]=[CH:37][C:36]2[CH:35]3[CH2:43][C:28]([CH2:27][N:24]4[CH2:23][CH2:22][C:21]([C:17]5[CH:18]=[N:19][CH:20]=[C:15]([CH2:14][OH:13])[CH:16]=5)([OH:44])[CH2:26][CH2:25]4)([C:29]4[C:34]3=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:41]=2[CH:40]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 21480582HCID 21480582, compound

Product 1

HCID 21480671HCID 21480671, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A tetrahydrofuran solution (15 mL) of 4-(5-(tert-butyldimethylsilyl)oxymethyl-3-pyridyl)-1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)piperidin-4-ol (1.70 g, 3.04 mmol) was cooled to 0° C. under nitrogen and treated with tetrabutylammonium fluoride (1.0N in tetrahydrofuran, 3.20 mL, 3.20 mmol, 1.05 eq). The reaction was warmed to room temperature and stirred at that temperature for 3 h. Water (15 mL) was added and the resulting aqueous phase was extracted with ethyl acetate (3×15 mL). Combined organic extracts were dried over anhydrous sodium sulfate, filtered, and reduced to an oil. This procedure resulted in 1.20 g (89%) of the title compound. TLC analysis (Rf 0.11, 5% methanol in diethyl ether). No additional purification was required. 1H NMR (CDCl3, 250 MHz) 8.62 (s, 1H), 8.42 (s, 1H), 7.84 (s, 1H), 7.21 (m, 4H), 6.94 (m, 3H), 4.69 (s, 2H), 4.27 (s, 1H), 3.44 (s, 2H), 2.90 (m, 2H), 2.74 (m, 2H), 2.62 (d, J=1.3 Hz, 2H), 2.11 (m, 2H), 1.76 (m, 2H) MS (CI, CH4) m/z 447 (M+1,100), 449 (32), 475 (M+29,19), 429 (71), 431 (25) The free base was dissolved in ether and acidified with ethereal HCl. The hydrochloride salt was filtered, rinsed with fresh ether and dried in vacuo (room temperature, 10 pascal, 18 h) to yield a white solid, mp 235°-240° C. (dec).

Workup

  1. extractionthe resulting aqueous phase was extracted with ethyl acetate (3×15 mL)
  2. dry with materialCombined organic extracts were dried over anhydrous sodium sulfate
  3. filtrationfiltered

Sources & evidence

ORD record
ord-1288185ce6c541ab823c80a33c1538f9
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

Loading…