Triphenylphosphine → tert-butyl 2-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethylcarbamate

HRID 1845727Notes

Reaction equation

HRID 1845727 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([OH:18])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:2].[C:19]([O:23][C:24](=[O:29])[NH:25][CH2:26][CH2:27]O)([CH3:22])([CH3:21])[CH3:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([O:18][CH2:27][CH2:26][NH:25][C:24](=[O:29])[O:23][C:19]([CH3:22])([CH3:21])[CH3:20])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:2]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 2733206tert-butyl N-(2-hydroxyethyl)carbamate2×HCID 5363146Diisopropyl azodicarboxylate2×HCID 574299842-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-ol

Product 1

HCID 68926789tert-butyl 2-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethylcarbamateYield 24.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred slurry of 2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-ol (3.80 g, 15.6 mmol), N-(2-hydroxyethyl)carbamic acid tert-butyl ester (3.9 g, 24 mmol), and triphenylphosphine (6.3 g, 24 mmol) in tetrahydrofuran (120 mL) at 0° C. was added diisopropylazodicarboxylate (4.7 mL, 24 mmol). After 1 hour, the solution was allowed to warm to room temperature. More N-(2-hydroxyethyl)carbamic acid tert-butyl ester (3.9 g, 24 mmol) and triphenylphosphine (6.3 g, 24 mmol) were added, then a solution of diisopropylazodicarboxylate (4.7 mL, 24 mmol) in tetrahydrofuran (10 mL). The reaction mixture was stirred over the weekend, then concentrated under reduced pressure. Dichloromethane (150 mL) was added and the solution was washed with water (2×25 mL). The organic layer was dried over potassium carbonate, filtered, and concentrated under reduced pressure. The solid was washed with diethyl ether/hexanes twice and dried to afford 1.5 g of crude tert-butyl 2-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethylcarbamate, which was used without purification in Part D below.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionDichloromethane (150 mL) was added
  3. washthe solution was washed with water (2×25 mL)
  4. dry with materialThe organic layer was dried over potassium carbonate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. washThe solid was washed with diethyl ether/hexanes twice
  8. customdried

Sources & evidence

ORD record
ord-2788365c89614c2da6d4653cb47432a4
Source dataset
uspto-grants-2015_02
Patent number
US08951528B2

Reaction notes

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