Ethanethiol → HCID 21480631, compound

HRID 1490212Notes

Reaction equation

HRID 1490212 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+]>O1CCCC1>[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 example 58) (2.00 g, 5.00 mmol, 1 eq) in tetrahydrofuran (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). Combined organic extracts were washed with water (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). 1H NMR (CDCl3, 250 HHz) 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 (CI, 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° C. (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. washCombined organic extracts were washed with water (2×100 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customThe reaction product was purified by flash chromatography over silica gel (200 mL, eluent: 50% ether in hexane)

Sources & evidence

ORD record
ord-9a554c649f4a40338c1255f0a39e7b04
Source dataset
uspto-grants-1997_10
Patent number
US05681840

Reaction notes

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