Hydrochloric Acid → (S)-2-nitro-6-(piperidin-3-ylmethoxy)benzonitrile hydrochloride

HRID 332941Notes

Reaction equation

HRID 332941 reaction equation
[C:1]([C:3]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][CH2:6][C@H:7]1[CH2:12][CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]1)#[N:2].[ClH:27]>O1CCOCC1>[ClH:27].[N+:24]([C:23]1[CH:22]=[CH:21][CH:20]=[C:4]([O:5][CH2:6][C@H:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[C:3]=1[C:1]#[N:2])([O-:26])=[O:25]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86714272(S)-tert-butyl 3-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate

Product 1

HCID 86714270(S)-2-nitro-6-(piperidin-3-ylmethoxy)benzonitrile hydrochlorideYield 89%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (S)-tert-butyl 3-((2-cyano-3-nitrophenoxy)methyl)piperidine-1-carboxylate (Example 1e, 41.74 g) in dioxane (115 mL) cooled to 0° C. in an ice bath was added a solution of 4N HCl in dioxane (70 mL, 280 mmol). The reaction mixture was stirred at room temperature overnight then evaporated under reduced pressure. Et2O (700 mL) was added to the residue and the suspension was refluxed for one hour. The solid was collected by filtration and dried under high vacuum to afford (S)-2-nitro-6-(piperidin-3-ylmethoxy)benzonitrile hydrochloride as a pale peach solid (24.64 g, 89% yield over two steps). 1H NMR (400 MHz, DMSO-d6) δ 1.47-1.30 (m, 1H). 1.77-1.62 (m, 1H), 1.84 (t, J=12.4 Hz, 2H), 2.32 (d, J=9.4 Hz, 1H), 2.87-2.68 (m, 2H), 3.27-3.16 (m, 2H), 4.15 (dd, J=9.7, 7.2 Hz, 1H), 4.25 (dd, J=9.7, 5.4 Hz, 1H), 7.72 (dd, J=7.6, 1.9 Hz, 1H), 7.96-7.86 (m, 2H), 9.20-8.89 (m, 2H). MS 262 (MH+).

Workup

  1. customthen evaporated under reduced pressure
  2. additionEt2O (700 mL) was added to the residue
  3. temperaturethe suspension was refluxed for one hour
  4. filtrationThe solid was collected by filtration
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-f675f3e007cd4c9285b22c388c3eba68
Source dataset
uspto-grants-2014_11
Patent number
US08877922B2

Reaction notes

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