Ethyl Acetate → HCID 178487961, compound

HRID 633802Notes

Reaction equation

HRID 633802 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[N:20]=2)[N:15]=[CH:14][C:13]=1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=O)OCC)C.[C:32]([O:36][C:37](=[O:48])[NH:38][C@H:39]1[CH2:44][CH2:43][C@H:42]([CH2:45][CH:46]=O)[CH2:41][CH2:40]1)([CH3:35])([CH3:34])[CH3:33].C(OCC)(=O)C>O1CCCC1>[C:32]([O:36][C:37](=[O:48])[NH:38][C@H:39]1[CH2:40][CH2:41][C@H:42]([CH2:45][CH:46]=[CH:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[N:20]=3)[N:15]=[CH:14][C:13]=2[O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:43][CH2:44]1)([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 86730697(3-Benzyloxy-6-methoxy-[1,5]naphthyridin-4-ylmethyl)-phosphonic acid diethyl esterHCID 178453924HCID 178453924, compound

Product 1

HCID 178487961HCID 178487961, compoundYield 131.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (86 mg, 1.91 mmol, 2.3 eq) is added at 0° C. to a stirred solution of (3-benzyloxy-6-methoxy-[1,5]naphthyridin-4-ylmethyl)-phosphonic acid diethyl ester (350 mg, 0.83 mmol, 1.0 eq) in tetrahydrofuran (30 mL) and the resulting mixture is stirred at 0° C. for 1 hour before the addition of a solution of [trans-4-(2-oxo-ethyl)-cyclohexyl]-carbamic acid tert-butyl ester (200 mg, 0.83 mmol, 1.0 eq) in tetrahydrofuran (5 mL). After 15 hours stirring at room temperature, the reaction mixture is quenched with ammonium chloride aqueous solution (20 mL), tetrahydrofuran is removed and the resulting residue is extracted with ethyl acetate (3×50 mL) and brine (50 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 10:1 to 6:1, v/v) to afford {trans-4-[3-(3-benzyloxy-6-methoxy-[1,5]naphthyridin-4-yl)-allyl]-cyclohexyl}-carbamic acid tert-butyl ester as a white solid (548 mg, 55% yield).

Workup

  1. customthe reaction mixture is quenched with ammonium chloride aqueous solution (20 mL), tetrahydrofuran
  2. customis removed
  3. extractionthe resulting residue is extracted with ethyl acetate (3×50 mL) and brine (50 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-9644d9f7c1344db39714d6cb1efc0ac4
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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