tert-Butyl acetate → benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate

HRID 470928

Reaction equation

HRID 470928 reaction equation
[OH:1][CH:2]([C:7]1[C:8]([CH3:34])=[N:9][C:10]2[CH2:11][CH2:12][N:13]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[CH2:14][C:15]=2[C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)[C:3]([O:5][CH3:6])=[O:4].C(O[C:39]([CH3:42])([CH3:41])[CH3:40])(=O)C>C(Cl)Cl>[C:39]([O:1][CH:2]([C:7]1[C:8]([CH3:34])=[N:9][C:10]2[CH2:11][CH2:12][N:13]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[CH2:14][C:15]=2[C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)[C:3]([O:5][CH3:6])=[O:4])([CH3:42])([CH3:41])[CH3:40]

Participants

4

Reactant 2

HCID 10908tert-Butyl acetateHCID 86692201benzyl 3-(1-hydroxy-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate2×

Product 1

HCID 86692202benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylateYield 73.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 3-(1-hydroxy-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (intermediate 11) (0.10 g, 0.217 mmol) in CH2Cl2 (3 ml) was added tert-butyl acetate (2.05 ml, 15.2 mmol) followed by HClO4 (0.056 ml, 0.651 mmol). The flask was sealed and stirred at room temperature for 2.5 h. The reaction was quenched with sat'd aq NaHCO3 (gas evolution). The organic phase was dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography (Biotage; 0%-30% EtOAc/hexanes). The product-containing fractions were combined and concentrated to give benzyl 3-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-2-methyl-4-(p-tolyl)-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate (82.4 mg, 72% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.01-7.78 (m, 9H), 5.13 (s, 2H), 4.97 (s, 1H), 4.29-4.32 (m, 1H), 4.05-4.10 (m, 1H), 3.78-3.81 (m, 2H), 3.71 (s, 3H), 3.06 (bs, 2H), 2.64 (s, 3H), 2.45 (s, 3H) 0.99 (s, 9H). LCMS (M+H) calcd for C31H37N2O5: 517.27. found: 517.4.

Workup

  1. customThe flask was sealed
  2. customThe reaction was quenched with sat'd aq NaHCO3 (gas evolution)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (Biotage; 0%-30% EtOAc/hexanes)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e1e2dac7a9684574be810775688814bb
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Linked notes

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