Ethanethiol → HCID 21480631, compound

HRID 1721807Notes

Reaction equation

HRID 1721807 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[C:25](F)=[N:26][CH:27]=[CH:28][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.[Na].[CH2:32]([SH:34])[CH3:33].[H-].[Na+]>C1COCC1>[CH:1]1[C:14]2[C:13]3([CH2:16][N:17]4[CH2:22][CH2:21][C:20]([C:24]5[C:25]([S:34][CH2:32][CH3:33])=[N:26][CH:27]=[CH:28][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

Participants

6

Reactant 4

HCID 6343Ethanethiol2×HCID 24758Sodium hydrideHCID 5360545SodiumHCID 12016072HCID 12016072, compound

Product 1

HCID 21480631HCID 21480631, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(2-fluoro-3-pyridyl)piperidin-4-ol (described in e. above) (2.00 g, 5.00 mmol, 1 eq) in THF (50 mL) under nitrogen was added the sodium salt of ethanethiol (0.90 g, 10.7 mmol, 2.2 eq). The thiolate salt was prepared from ethanethiol and sodium hydride under standard conditions. The reaction was heated to reflux for 18 h and quenched by pouring into water (100 mL). The aqueous phase was extracted with diethyl ether (2×100 mL), dried over anhydrous sodium sulfate, filtered, and reduced to an oil. The reaction product was purified by flash chromatography over silica gel (200 mL, eluent: 50% ether in hexane) to yield 2.00 g (90%) of the title compound. TLC analysis (Rf 0.29, 50% ether in hexane). 1HNMR (CDCl3, 250 MHz) 8.35 (dd, J=1.6, 4.7 Hz, 1H), 7.58 (dd, J=1.7, 7.7 Hz, 1H), 7.22 (m, 4H), 6.95 (m, 5H), 4.27 (s, 1H), 3.58 (s, 1H), 3.48 (s, 2H), 3.28 (q, J=7.3 Hz, 2H), 2.89 (m, 2H), 2.80 (ddd, J=9.3, 14.9, 10.7 Hz, 2H) 2.62 (d, J=1.5 Hz, 2H), 2.12 (m, 4H), 1.35 (t, J=7.2 Hz, 3H) MS (Cl, CH4) m/z 443 (M+1,100), 471 (M+29,16), 425 (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 176-179 (dec).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 18 h
  3. customquenched
  4. additionby pouring into water (100 mL)
  5. extractionThe aqueous phase was extracted with diethyl ether (2×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe reaction product was purified by flash chromatography over silica gel (200 mL, eluent: 50% ether in hexane)

Sources & evidence

ORD record
ord-57d5a8cf6527409da9f5f2aab439bea0
Source dataset
uspto-grants-1996_04
Patent number
US05512575

Reaction notes

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