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

HRID 1422947Notes

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]

Participants

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

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

Sources & evidence

ORD record: ord-175e548234f14d949e6b37ff7f62846a
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927541B2

Reaction notes

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