tert-Butyldimethylsilyl chloride → 6-(((Tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

HRID 1777886Notes

Reaction equation

HRID 1777886 reaction equation
[CH3:1][O:2][CH:3]([O:16][CH3:17])[C:4]1[C:13]([CH2:14][OH:15])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.CCN(C(C)C)C(C)C.[C:27]([Si:31](Cl)([CH3:33])[CH3:32])([CH3:30])([CH3:29])[CH3:28].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Si:31]([O:15][CH2:14][C:13]1[CH:12]=[C:11]2[C:6](=[N:5][C:4]=1[CH:3]([O:2][CH3:1])[O:16][CH3:17])[NH:7][CH2:8][CH2:9][CH2:10]2)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:33])[CH3:32]

Participants

8

Reactant 4

HCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 1180364762-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-methanol2×

Product 1

HCID 1317347776-(((Tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methanol (intermediate 40, 6.5 g, 27.3 mmol) in DCM (100 ml) and DMF (25 ml) at 0° C. were added DIPEA (7.15 ml, 40.9 mmol), tert-butylchlorodimethylsilane (4.93 g, 32.7 mmol) and DMAP (0.067 g, 0.546 mmol). The reaction mixture was then stirred for 1 h at room temperature, then poured into sat. aq. NaHCO3 and extracted twice with DCM. The combined organic phases were dried over Na2SO4, filtered and evaporated. The crude material was purified by normal phase chromatography (120 g silica gel cartridge, heptanes/EtOAc 95:5 to 0:100) to give the title compound as a light yellow oil which solidified upon standing to give an off-white powder. (UPLC-MS 3) tR 1.10 min; ESI-MS 353.3 [M+H]+.

Workup

  1. extractionextracted twice with DCM
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude material was purified by normal phase chromatography (120 g silica gel cartridge, heptanes/EtOAc 95:5 to 0:100)

Sources & evidence

ORD record
ord-ea6210f79f8f4e2da5721f5ea2c191a7
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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