Hydroxylamine → 4-(tert-Butyl-dimethyl-silanyloxymethyl)-3-methyl-pyridin-2-ylamine

HRID 1814000Notes

Reaction equation

HRID 1814000 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C:8]1[CH:13]=[CH:12][N:11]=[C:10](Cl)[C:9]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2].CC([O-])(C)C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=[NH:83])(C1C=CC=CC=1)C1C=CC=CC=1.NO>C(OCC)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:1]([SiH2:5][O:6][C:7]([CH3:17])([CH3:16])[C:8]1[CH:13]=[CH:12][N:11]=[C:10]([NH2:83])[C:9]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 787Hydroxylamine2×HCID 136809Benzophenone imineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 1317248164-(tert-Butyl-dimethyl-silanyloxymethyl)-2-chloro-3-methyl-pyridine

Product 1

HCID 1317248154-(tert-Butyl-dimethyl-silanyloxymethyl)-3-methyl-pyridin-2-ylamine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

An oven dried flask under N2 was charged with 4-(tert-butyl-dimethyl-silanyloxymethyl)-2-chloro-3-methyl-pyridine (10-1, 1.00 g, 3.68 mmol), NaOtBu (0.495 g, 5.15 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.067 g, 0.070 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.137 g, 0.22 mmol) and anhydrous toluene (10 mL). Benzophenone imine (0.740 mL, 4.41 mmol) was added and the reaction was heated to 80° C. After 3 hours the reaction was allowed to cool to room temperature and was diluted with 50 mL of diethyl ether. The resulting mixture was filtered through celite, washing with ether. The filtrate was concentrated, redissolved in 10 mL MeOH and hydroxylamine (50% aqueous, 0.676 mL, 11.0 mmol) was added. After stirring overnight, an additional 0.680 mL of hydroxylamine solution was added. After 8 hours the solution was concentrated in vacuo. The residue was purified by flash column chromatography (sample was loaded in DCM and eluted with a DCM to 9:1 DCM/MeOH gradient) to afford the title product. 1H NMR indicates that product is contaminated with BINAP dioxide. 1H NMR (CDCl3) δ 7.80 (d, 1H), 6.85 (d, 1H), 4.65 (s, 2H), 4.35 (bs, 2H), 2.00 (s, 3H), 0.95 (s, 9H), 0.15 (s, 6H).

Workup

  1. customAn oven dried flask under N2
  2. temperatureto cool to room temperature
  3. filtrationThe resulting mixture was filtered through celite
  4. washwashing with ether
  5. concentrationThe filtrate was concentrated
  6. dissolutionredissolved in 10 mL MeOH
  7. concentrationAfter 8 hours the solution was concentrated in vacuo
  8. customThe residue was purified by flash column chromatography (sample
  9. washeluted with a DCM to 9:1 DCM/MeOH gradient)

Sources & evidence

ORD record
ord-2674d8dbfa814f9982fe7e06fb99024c
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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