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tert-Butanol → (4-Benzyloxy-6-methoxy-[1,5]naphthyridin-3-yl)-carbamic acid tert-butyl ester

HRID 2273235
Notes
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Reaction equation

HRID 2273235 reaction equation
C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])C=CC=CC=1.[CH2:18]([O:25][C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[N:34]=2)[N:29]=[CH:28][C:27]=1C(O)=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C:41]([OH:45])([CH3:44])([CH3:43])[CH3:42].C([N:48]([CH2:51]C)CC)C>CN(C)C=O>[C:41]([O:45][C:51](=[O:8])[NH:48][C:27]1[CH:28]=[N:29][C:30]2[C:35]([C:26]=1[O:25][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[N:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)([CH3:44])([CH3:43])[CH3:42]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 672550274-Benzyloxy-6-methoxy-[1,5]naphthyridine-3-carboxylic acid

Product 1

HCID 67255694(4-Benzyloxy-6-methoxy-[1,5]naphthyridin-3-yl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Conditions

Temperature
100 °C

Procedure

Diphenylphosphoryl azide (25.0 mL, 116.0 mmol, 1.5 eq) is added at room temperature to a stirred solution of 4-benzyloxy-6-methoxy-[1,5]naphthyridine-3-carboxylic acid (24.0 g, 77.34 mmol, 1.0 eq) in N,N-dimethylformamide (300 mL), followed by tert-butanol (8.5 mL, 89.71 mmol, 1.16 eq) and triethylamine (104.5 mL, 773.4 mmol, 10.0 eq). After 30 minutes stirring at 70° C. and 2 hours at 100° C., the reaction mixture is cooled down to room temperature, solvent is removed and the residue is extracted with ethyl acetate (3×200 mL) and a saturated sodium hydrogen carbonate aqueous solution (200 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to afford crude (4-benzyloxy-6-methoxy-[1,5]naphthyridin-3-yl)-carbamic acid tert-butyl ester that is directly engaged in the next step.

Workup

  1. temperaturethe reaction mixture is cooled down to room temperature
  2. customsolvent is removed
  3. extractionthe residue is extracted with ethyl acetate (3×200 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-3bcfd68865c24fb8b2146bd07110ea01
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09120822B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes