Acetic Acid → 2-((S)-3-Methoxy-pyrrolidin-1-ylmethyl)-5-nitro-pyridine

HRID 55876Notes

Reaction equation

HRID 55876 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:10]=O)=[N:8][CH:9]=1)([O-:3])=[O:2].[CH3:12][O:13][C@H:14]1[CH2:18][CH2:17][NH:16][CH2:15]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCl.O>[CH3:12][O:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH2:10][C:7]2[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=2)[CH2:15]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 151455015-Nitropyridine-2-carbaldehydeHCID 26191850(S)-3-Methoxypyrrolidine

Product 1

HCID 903587862-((S)-3-Methoxy-pyrrolidin-1-ylmethyl)-5-nitro-pyridineYield 40.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 31 (0.4 g, 2.6 mmol) and (S)-3-methoxy-pyrrolidine (0.4 g, 3.2 mmol) in dichloromethane (10 mL) was added acetic acid (0.01 mL, 0.25 mmol). After 30 minutes, sodium triacetoxyborohydride (1.1 g, 5.3 mmol) was added to the above mixture and stirred at rt for 15 minutes. The reaction mixture was diluted with water (10 mL), treated with saturated NaHCO3 solution to get pH˜8 and extracted with dichloromethane (2×20 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4) and evaporated. The crude compound was purified by silica gel flash chromatography, eluting with 2% MeOH/DCM to afford 32 (0.25 g, 40%) as a liquid. Rf: 0.3 (5% MeOH/DCM); (m/z): 238 [MH]+; 1H NMR (400 MHz, DMSO-d6): δ 9.28 (1H, d, J=2.8 Hz), 8.59-8.56 (1H, m), 7.71 (1H, d, J=8.8 Hz), 3.93-3.80 (3H, m), 3.16 (3H, s), 2.73-2.62 (2H, m), 2.56-2.53 (1H, m), 2.50-2.47 (1H, m), 2.06-2.02 (1H, m), 1.72-1.65 (1H, m).

Workup

  1. customto get pH˜8
  2. extractionextracted with dichloromethane (2×20 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customThe crude compound was purified by silica gel flash chromatography
  7. washeluting with 2% MeOH/DCM

Sources & evidence

ORD record
ord-ab8856eea521480b9b0e866401f79422
Source dataset
uspto-grants-2016_09
Patent number
US09433622B2

Reaction notes

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