Ammonium Chloride → 1-{2-[4-(8-Fluoro-2-methoxy-5H-6-thia-chrysen-5-yl)-phenoxy]-ethyl}-piperidine

HRID 1513977Notes

Reaction equation

HRID 1513977 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH3:19])[CH:14]=3)[C:9]=2[C:20]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:24][CH:23]=2)=O)=[C:4]([S:37]C)[CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+].C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.C(=O)(O)[O-].[Na+]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[C:8]1[C:9](=[C:10]3[C:15](=[CH:16][CH:17]=1)[CH:14]=[C:13]([O:18][CH3:19])[CH:12]=[CH:11]3)[CH:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)=[CH:24][CH:23]=1)[S:37]2

Participants

8

Reactant 6

HCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chloride2×HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 21226445Aluminium lithium hydrideHCID 57552520[2-(4-Fluoro-2-methylsulfanyl-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Product 1

HCID 114548221-{2-[4-(8-Fluoro-2-methoxy-5H-6-thia-chrysen-5-yl)-phenoxy]-ethyl}-piperidineYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolve [2-(4-fluoro-2-methylsulfanyl-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone (1.2 g, 2.2 mmol) in dry THF (20 mL). Add lithium aluminum hydride (1M in THF, 2.3 mL, 2.3 mmol) dropwise. After 10 minutes slowly pour the black solution into saturated aqueous ammonium chloride and extract with methylene chloride twice. Dry the combined organic layers with sodium sulfate, filter and concentrate to yield a 2:1 mixture of rotational diastereomers. Dissolve the crude foam in dry THF (15 mL). Add diisopropylethylamine (2.5 mL, 14.4 mmol) and methanesulfonyl chloride (0.45 mL, 5.8 mmol) and heat to reflux under nitrogen. Add more methanesulfonyl chloride (0.45 mL, 5.8 mmol) after 2 hours to drive the reaction to completion. Pour the reaction into saturated aqueous sodium bicarbonate and extract twice with methylene chloride. Dry the combined organic layers with sodium sulfate, filter and concentrate. Purify the residue on silica gel (0% to 3% methanol in methylene chloride) to yield 440 mg (44%) of the title compound: mass spectrum (ion spray) m/z=500.3 (M+H).

Workup

  1. extractionextract with methylene chloride twice
  2. dry with materialDry the combined organic layers with sodium sulfate
  3. filtrationfilter
  4. concentrationconcentrate
  5. customto yield
  6. additiona 2:1 mixture of rotational diastereomers
  7. temperatureto reflux under nitrogen
  8. customthe reaction to completion
  9. additionPour
  10. extractionextract twice with methylene chloride
  11. dry with materialDry the combined organic layers with sodium sulfate
  12. filtrationfilter
  13. concentrationconcentrate
  14. customPurify the residue on silica gel (0% to 3% methanol in methylene chloride)

Sources & evidence

ORD record
ord-c8e2bac210194d9bab0aa25d66d82c3c
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…