Acetic Acid → 4-((5-Bromopyridin-2-yl)methyl)morpholine

HRID 2410862Notes

Reaction equation

HRID 2410862 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Br:15][C:16]1[CH:17]=[CH:18][C:19]([CH:22]=O)=[N:20][CH:21]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C(O)(=O)C>ClCCCl.CCOC(C)=O>[Br:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:22][N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[N:20][CH:21]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 98775625-Bromopyridine-2-carbaldehyde

Product 1

HCID 120852844-((5-Bromopyridin-2-yl)methyl)morpholineYield 39%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium triacetoxyborohydride (1.6 gm, 7.5 mmol) was added to a solution of 5-bromopicolinaldehyde (1.0 g, 5.4 mmol) and morpholine (0.54 g, 6.2 mmol) in 1,2-dichloroethane (10 mL) and this was left stirring for 2 hr. Acetic acid (0.35 mL, 6.2 mmol) was added and the reaction was left stirring over the weekend. It was diluted with EtOAc and washed with sat. aq. NaHCO3 followed by brine. This was concentrated, captured on a SCX column, washed with MeOH, and released with 2 N NH3 in MeOH to give 4-((5-bromopyridin-2-yl)methyl)morpholine (537 mg, 2.09 mmol, 39% yield) as a brown oil. MS (ESI) m/z 256.96 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.61 (1H, d, J=2.44 Hz), 7.77 (1H, dd, J=8.24, 2.44 Hz), 7.33 (1H, d, J=8.24 Hz), 3.67-3.77 (4H, m), 3.60 (2H, s), 2.42-2.57 (4H, m).

Workup

  1. waitthis was left
  2. waitthe reaction was left
  3. stirringstirring over the weekend
  4. washwashed with sat. aq. NaHCO3
  5. concentrationThis was concentrated
  6. washwashed with MeOH

Sources & evidence

ORD record
ord-e3db3381ba054a52b1f606ad348c7301
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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