Acetic Acid → HCID 59717871, compound

HRID 2224712Notes

Reaction equation

HRID 2224712 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[CH2:17]([NH2:22])[CH2:18][CH:19]([CH3:21])[CH3:20].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C>ClCCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13][NH:22][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7894IsoamylamineHCID 5049666Sodium triacetoxyborohydrideHCID 59717850HCID 59717850, compound

Product 1

HCID 59717871HCID 59717871, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-(5-Bromo-pyridin-2-yloxy)-benzaldehyde (RH3-A02640-038) (3.501 g, 12.6 mmol) in 1,2-dichloroethane (61 mL) is added isoamylamine (1.65 mL, 14.2 mmol), NaBH(OAc)3 (4.00 g, 18.9 mmol), and acetic acid (1.10 mL, 19.2 mmol). The reaction is stirred overnight. The reaction mixture is then washed with saturated NaHCO3 (2×100 mL), dried over MgSO4, filtered, and concentrated. The mixture is loaded on silica gel, eluted with hexanes with a gradient from 25% of ethyl acetate to 100% of ethyl acetate to give [4-(5-Bromo-pyridin-2-yloxy)-benzyl]-(3-methyl-butyl)-amine (2.18 g, 50%) as a yellow oil. 1NMR (400 MHz, CDCl3) δ ppm: 8.21 (d, J=3.1 Hz, 1H), 7.75 (dd, J=2.6, 8.7 Hz, 1H), 7.37-7.34 (m, 2H), 7.09-7.05 (m, 2H), 6.82 (d, J=9.1 Hz, 1H), 2.49 (s, 2H), 2.66 (dd, J=7.6, 7.6 Hz, 2H), 1.67-1.61 (m, 1H), 1.44-1.38 (m, 2H), 1.15 (s br, 1H), 0.90 (d, J=6.6 Hz, 6H); MS (ES): [M+H]+ found 261.7. Step 3 N-(6-{4-[(3-Methyl-butylamino)-methyl]-phenoxy}-pyridin-3-yl)-acetamide

Workup

  1. washThe reaction mixture is then washed with saturated NaHCO3 (2×100 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. washeluted with hexanes with a gradient from 25% of ethyl acetate to 100% of ethyl acetate

Sources & evidence

ORD record
ord-e04e91e704e443ba92a576c4836fa49c
Source dataset
uspto-grants-2008_05
Patent number
US07378448B2

Reaction notes

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