Water → benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2',3,3'-tetrahydro-1H,1'H-spiro[1,8-naphthyridine-4,4'-pyridine]-1'-carboxylate

HRID 1664801Notes

Reaction equation

HRID 1664801 reaction equation
Br[C:2]1[C:3]([N:8]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:9](=[O:27])[CH2:10][C:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:15][CH:16]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C1(C(N)C2CCCCC2)CCCCC1.O>O1CCOCC1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[O:27]=[C:9]1[CH2:10][C:11]2([CH:12]=[CH:13][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:15][CH2:16]2)[C:2]2[C:3](=[N:4][CH:5]=[CH:6][CH:7]=2)[N:8]1[CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 3

HCID 962WaterHCID 10774245alpha-CyclohexylcyclohexanemethanamineHCID 59555191benzyl 4-[2-((3-bromopyridin-2-yl){[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 57663850benzyl 2-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-2,2',3,3'-tetrahydro-1H,1'H-spiro[1,8-naphthyridine-4,4'-pyridine]-1'-carboxylateYield 78.8%

Reagents, catalysts & solvents 2

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)Catalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Bis(tri-t-butylphosphine) palladium(0) (9.0 mg, 0.018 mmol) was added to solution of benzyl 4-[2-((3-bromopyridin-2-yl){[2-(trimethylsilyl)ethoxy]methyl}amino)-2-oxoethyl]-3,6-dihydropyridine-1(2H)-carboxylate (0.10 g, 0.18 mmol) and dicyclohexylmethylamine (42 μL, 0.196 mmol) in dioxane (2 mL). After 5 min, the reaction mixture was heated to 50° C. After 1.5 h, additional bis(tri-t-butylphosphine) palladium(0) (9.0 mg, 0.018 mmol) was added. After 20 min, water was added and the mixture was extracted with ether (2×). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (95% hexanes/ethyl acetate→40% hexanes/ethyl acetate) gave the title compound (68 mg). MS 480.2 (M+1).

Workup

  1. waitAfter 1.5 h
  2. waitAfter 20 min
  3. extractionthe mixture was extracted with ether (2×)
  4. dry with materialThe combined organic extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (95% hexanes/ethyl acetate→40% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-89a1e3e66f6a4529ac40e8eabe0969e0
Source dataset
uspto-grants-2011_10
Patent number
US08039460B2

Reaction notes

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