Hydrochloric Acid → HCID 66673584, compound

HRID 423686Notes

Reaction equation

HRID 423686 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:17]=[CH:16][C:15]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21]3)=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].[C:33]([OH:39])([C:35]([F:38])([F:37])[F:36])=[O:34]>O1CCOCC1>[C:33]([OH:39])([C:35]([F:38])([F:37])[F:36])=[O:34].[F:36][C:35]([F:38])([F:37])[C:33]([OH:39])=[O:34].[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[CH:16][N:17]=2)=[CH:8][CH:7]=1)(=[O:4])=[O:5]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 6422Trifluoroacetic acidHCID 249943331,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Product 2

HCID 6422Trifluoroacetic acidYield 0.05%HCID 66673584HCID 66673584, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Procedure

4N HCl in 1,4-dioxane (1 mL) was added to a mixture of 1,1-dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (462 mg, 1.03 mmol) in 1,4-dioxane (10 mL) at ambient temperature. The mixture was stirred at ambient temperature overnight. The mixture was charged with additional 4N HCl in 1,4-dioxane (1 mL), and stirred at ambient temperature overnight. The mixture was then charged with TFA (2 mL), and stirred at ambient temperature for 4 h. The mixture was concentrated, diluted with water, basified with saturated NaHCO3, and extracted with EtOAc. The organics were dried over MgSO4, filtered, and the filtrate was concentrated. The crude product was purified by reverse-phase preparative HPLC using CH3CN:H2O gradient (5:95 to 75:25) with 0.05% TFA as a modifier to give 107 mg (23%) of 2-[4-(methylsulfonyl)phenyl]-5-[(4-piperidinylmethyl)oxy]pyridine trifluoroacetate as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.59-8.50 (m, 1H), 8.44 (d, 1H, J=2.9 Hz), 8.28 (d, 2H, J=8.6 Hz), 8.08 (d, 1H, J=8.8 Hz), 8.00 (d, 2H, J=8.6 Hz), 7.55 (dd, 1H, Ja=8.8 Hz, Jb=3.0 Hz), 4.04 (d, 2H, J=6.2 Hz), 3.40-3.25 (m, 2H), 3.25 (s, 3H), 3.00-2.86 (m, 2H), 2.16-2.06 (m, 1H), 2.05-1.90 (m, 2H), 1.56-1.40 (m, 2H); LRMS (ESI), m/z 347 (M+H).

Workup

  1. stirringstirred at ambient temperature overnight
  2. stirringstirred at ambient temperature for 4 h
  3. concentrationThe mixture was concentrated
  4. additiondiluted with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customThe crude product was purified by reverse-phase preparative HPLC

Sources & evidence

ORD record
ord-0beba2f7ad08408a9e9aafb117a82153
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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