2-Amino-5-methylpyridine → HCID 57504589, compound

HRID 1098105Notes

Reaction equation

HRID 1098105 reaction equation
C([Li])CCC.[CH3:6][C:7]1[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=1.[Si:14]([O:21][C@H:22]([CH2:27][O:28][CH3:29])[C:23](OC)=[O:24])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1COCC1.CCOC(C)=O>[Si:14]([O:21][C@H:22]([CH2:27][O:28][CH3:29])[C:23]([NH:13][C:10]1[CH:9]=[CH:8][C:7]([CH3:6])=[CH:12][N:11]=1)=[O:24])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16]

Participants

6

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 59279515HCID 59279515, compoundHCID 178418339Butyllithium

Product 1

HCID 57504589HCID 57504589, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
10 °C

Procedure

A solution of n-butyllithium (2.5M in hexanes) (2.04 mL, 3.26 mmol) was added dropwise to a stirred solution of 5-methylpyridin-2-amine (CAS 1603-41-4) (353 mg, 3.26 mmol) in THF (10 mL) cooled to 10° C. under nitrogen. The resulting solution was stirred at ambient temperature for 10 minutes and then added to a solution of (R)-methyl 2-(tert-butyldimethylsilyloxy)-3-methoxypropanoate C5b (810 mg, 3.26 mmol) in THF (10 mL) at 10° C. The resulting solution was stirred at ambient temperature for 1 hour. The reaction mixture was diluted with EtOAc (75 mL) and washed sequentially with saturated ammonium chloride (50 mL), water (25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. Purification by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane provided (R)-2-(tert-butyldimethylsilyloxy)-3-methoxy-N-(5-methylpyridin-2-yl)propanamide (300 mg). 1H NMR (400 MHz, CDCl3) δ 0.15 (3H, s), 0.16 (3H, s), 0.88 (9H, s), 2.12 (3H, s), 3.46 (3H, s), 3.61-3.65 (2H, m), 4.35-4.42 (1H, m), 7.47 (1H, d), 8.19 (1H, d), 8.20 (1H, s), 8.97 (1H, s), m/z (ESI+) (M+H)+=325; HPLC tR=3.08 min.

Workup

  1. stirringThe resulting solution was stirred at ambient temperature for 1 hour
  2. washwashed sequentially with saturated ammonium chloride (50 mL), water (25 mL) and saturated brine (25 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customPurification
  8. washby flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-ed45c3816b1d4ab89e797cb7c7be6ee9
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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