Hydrochloric Acid → tert-Butyl (2-chloropyridin-3-yl)carbamate

HRID 2382092Notes

Reaction equation

HRID 2382092 reaction equation
[NH2:1][C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:19](C(OC(C)(C)C)=O)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=O.Cl>C1COCC1>[C:23]([O:22][C:20](=[O:19])[NH:1][C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 805282-Chloro-3-pyridylamineHCID 90495Di-tert-butyl dicarbonateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 11961738tert-Butyl (2-chloropyridin-3-yl)carbamateYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 3-amino-2-chloropyridine (5 g 38.9 mmol) in THF (35 mL) is added 2 M NaHMDS in THF (38.9 mL, 77.8 mmol). After stirring at rt for 15 min, BOC2O (7.7 g, 35.6 mmol) in THF (20 mL) is added in one portion and then stirred for 5 h at rt. 0.1% aqueous HCl is added. The mixture is extracted with EtOAc. The organic layer is dried (Na2SO4), filtered and concentrated. The residue is chromatographed through silica gel eluting with 0-50% EtOAc in heptane to afford (2-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (7.18 g, 89%). MS: 229 (M+H); 1H NMR (300 MHz, CDCl3): δ 8.52 (d, 1H), 8.05 (dd, 1H), 7.23 (dd, 1H), 7.02 (broad s, 1H), 1.55 (s, 9H)).

Workup

  1. stirringstirred for 5 h at rt
  2. extractionThe mixture is extracted with EtOAc
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is chromatographed through silica gel eluting with 0-50% EtOAc in heptane

Sources & evidence

ORD record
ord-ef04e1705bfb4be3ab5658b28f4931f6
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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