Diphenyl carbonate → HCID 118037025, compound

HRID 1777911Notes

Reaction equation

HRID 1777911 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:11][CH:12]([F:28])[C:13]1[CH:14]=[C:15]2[C:20](=[N:21][C:22]=1[CH:23]([O:26][CH3:27])[O:24][CH3:25])[NH:19][CH2:18][CH2:17][CH2:16]2.[C:29]1([O:35][C:36](=O)[O:37]C2C=CC=CC=2)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[F:28][CH:12]([F:11])[C:13]1[CH:14]=[C:15]2[C:20](=[N:21][C:22]=1[CH:23]([O:24][CH3:25])[O:26][CH3:27])[N:19]([C:36]([O:35][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:37])[CH2:18][CH2:17][CH2:16]2

Participants

5

Reactant 3

HCID 7597Diphenyl carbonateHCID 2733832Lithium HexamethyldisilazideHCID 118037108HCID 118037108, compound2×

Product 1

HCID 118037025HCID 118037025, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of LHMDS in THF (1.6M, 6.64 ml, 10.63 mmol) was added drop wise to a solution of 6-(difluoromethyl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 101, 1.7 g, 6.25 mmol) and diphenylcarbonate (1.41 g, 6.57 mmol) in THF (20 ml) at −78° C. The reaction mixture was stirred for 30 minutes at −78° C., then for 18 h at room temperature, partitioned between saturated aqueous NH4Cl and DCM, extracted DCM (2×), dried over Na2SO4 and evaporated. The residue was preabsorbed onto isolate and purified by normal phase chromatography using a 40 g RediSep® silica column, eluting with a gradient from heptane to 50% EtOAc in heptane. Product containing fractions were combined and evaporated to give the title compound as a white solid. (UPLC-MS 7) tR 1.19 min; ESI-MS 379.4 [M+H]+.

Workup

  1. waitfor 18 h at room temperature
  2. custompartitioned between saturated aqueous NH4Cl and DCM
  3. extractionextracted DCM (2×)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe residue was preabsorbed
  7. customonto isolate
  8. custompurified by normal phase chromatography
  9. washeluting with a gradient from heptane to 50% EtOAc in heptane
  10. additionProduct containing fractions
  11. customevaporated

Sources & evidence

ORD record
ord-4b40231a658a480e849996c84cfd2ba6
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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