Ethyl Acetate → Methyl 6-chloro-5-isothiocyanatonicotinate

HRID 1426162

Reaction equation

HRID 1426162 reaction equation
[C:1](Cl)(Cl)=[S:2].[NH2:5][C:6]1[C:7]([Cl:16])=[N:8][CH:9]=[C:10]([CH:15]=1)[C:11]([O:13][CH3:14])=[O:12].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>ClCCl>[Cl:16][C:7]1[C:6]([N:5]=[C:1]=[S:2])=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][N:8]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10040ThiophosgeneHCID 10340Sodium CarbonateHCID 18412438Methyl 5-amino-6-chloropyridine-3-carboxylate

Product 1

HCID 86639699Methyl 6-chloro-5-isothiocyanatonicotinateYield 76.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Thiophosgene (6.367 g, 55.37 mmol) in dichloromethane (10 mL) was added to a mixture of methyl 5-amino-6-chloronicotinate (8.61 g, 46.14 mmol) and sodium carbonate (9.781 g, 92.29 mmol) in dichloromethane (200 mL). The reaction mixture was stirred for four days at ambient temperature. The reaction mixture was washed with water and brine, dried, and concentrated. The residue was purified via MPLC (Biotage) eluting with 12:1 hexane:ethyl acetate to afford methyl 6-chloro-5-isothiocyanatonicotinate (8.03 g, 76.1% yield) as a white solid: 1H NMR (CDCl3) δ 3.97 (s, 3H), 8.09 (s, 1H), 8.84 (s, 1H).

Workup

  1. washThe reaction mixture was washed with water and brine
  2. customdried
  3. concentrationconcentrated
  4. customThe residue was purified via MPLC (Biotage)
  5. washeluting with 12:1 hexane

Sources & evidence

ORD record
ord-0a7ff6a18d04445fb83ada702e8df418
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Linked notes

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