Potassium Carbonate → Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate

HRID 470920Notes

Reaction equation

HRID 470920 reaction equation
[C:1]([O:5][CH:6]([C:11]1[C:12]([CH:36]([CH3:38])[CH3:37])=[N:13][C:14]2[C:15]([CH3:35])([CH3:34])[CH2:16][N:17](C(=O)C(F)(F)F)[CH2:18][C:19]=2[C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+]>CO.CCOCC>[C:1]([O:5][CH:6]([C:11]1[C:12]([CH:36]([CH3:38])[CH3:37])=[N:13][C:14]2[C:15]([CH3:35])([CH3:34])[CH2:16][NH:17][CH2:18][C:19]=2[C:20]=1[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 86692193Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2,2,2-trifluoroacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate2×

Product 1

HCID 86692192Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetateYield 57%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2,2,2-trifluoroacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 4) (0.250 g, 0.464 mmol) and K2CO3 (0.064 g, 0.464 mmol) in MeOH was stirred at room temperature for 24 h. The reaction was diluted with Et2O (50 mL), washed with water (10 mL), brine (10 mL), dried (Na2SO4), filtered and concentrated to give a pale yellow residue which was purified by reverse phase preparative-HPLC, eluting with MeCN/H2O, to afford methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (0.117 g, 57% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.28-7.32 (1H, m), 7.15-7.20 (1H, m), 7.13 (2H, d, J=6.7 Hz), 4.79 (1H, s), 3.75 (1H, d, J=16.2 Hz), 3.69 (3H, s), 3.48 (1H, quin, J=6.6 Hz), 3.42 (1H, d, J=16.5Hz), 2.94-3.05 (2H, m), 2.17 (1H, br. s.), 1.39 (6H, s), 1.26 (3H, d, J=6.4 Hz), 1.09 (3H, d, J=6.7 Hz), 0.95 (9H, s). LCMS (M+H) calcd for C26H36FN2O3: 443.2. found: 433.3.

Workup

  1. washwashed with water (10 mL), brine (10 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a pale yellow residue which
  6. customwas purified by reverse phase preparative-HPLC
  7. washeluting with MeCN/H2O

Sources & evidence

ORD record
ord-f77aec5f5d8e4790a4cc7865566b9f35
Source dataset
uspto-grants-2014_01
Patent number
US08629276B2

Reaction notes

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