Ethyl chloroformate → HCID 86705398, compound

HRID 707486Notes

Reaction equation

HRID 707486 reaction equation
[H-].[Na+].[NH2:3][C:4]1[N:11]=[CH:10][C:9]([CH2:12][N:13]2[CH2:18][C@@H:17]([CH3:19])[O:16][C@@H:15]([CH3:20])[CH2:14]2)=[CH:8][C:5]=1[C:6]#[N:7].Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(=O)(O)[O-].[Na+]>C1COCC1>[C:6]([C:5]1[C:4]([NH:3][C:22](=[O:23])[O:24][CH2:25][CH3:26])=[N:11][CH:10]=[C:9]([CH2:12][N:13]2[CH2:14][C@@H:15]([CH3:20])[O:16][C@@H:17]([CH3:19])[CH2:18]2)[CH:8]=1)#[N:7]

Participants

6

Reactant 4

HCID 10928Ethyl chloroformateHCID 24758Sodium hydride2×HCID 516892Sodium BicarbonateHCID 86705399HCID 86705399, compound

Product 1

HCID 86705398HCID 86705398, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride in mineral oil (60%, 25 mg, 0.61 mmol) was added to 2-amino-5-(((2S,6R)-2,6-dimethylmorpholino)methyl)nicotinonitrile (100 mg, 0.41 mmol) in THF (2 mL) and the mixture was stirred for 5 minutes. Ethyl chloroformate (0.05 ml, 0.48 mmol) was added followed by additional sodium hydride (16 mg, 0.41 mmol) and the reaction stirred at room temperature for 3 hours. The reaction was poured into a saturated solution of sodium bicarbonate (10 mL), extracted with ethyl acetate (3×5 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was taken up in methanol (10 mL) and stirred with potassium carbonate (170 mg) for 10 minutes. It was then poured into saturated sodium bicarbonate (10 mL) and extracted with ethyl acetate (3×5 mL). The extracts were dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by flash chromatography, eluting with ethyl acetate in hexanes gave the title compound as a white powder (104 mg, 80%). 1H NMR (400 MHz, DMSO-d6) δ 1.04 (d, J=6.27 Hz, 6H), 1.26 (t, J=7.03 Hz, 3H), 1.69 (t, J=10.60 Hz, 2H), 2.67 (d, J=10.67 Hz, 2H), 3.51 (s, 2H), 3.54-3.62 (m, 2H), 4.17 (q, J=7.11 Hz, 2H), 8.12-8.24 (m, 1H), 8.56 (d, J=2.01 Hz, 1H), 10.37 (s, 1H).

Workup

  1. stirringthe reaction stirred at room temperature for 3 hours
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. stirringstirred with potassium carbonate (170 mg) for 10 minutes
  6. additionIt was then poured into saturated sodium bicarbonate (10 mL)
  7. extractionextracted with ethyl acetate (3×5 mL)
  8. dry with materialThe extracts were dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography
  11. washeluting with ethyl acetate in hexanes

Sources & evidence

ORD record
ord-8a2af3d4e28248aabeef5caa1b218f2b
Source dataset
uspto-grants-2015_11
Patent number
US09175010B2

Reaction notes

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