Hydrochloric Acid → tert-Butyl (4-chloropyridin-3-yl)carbamate

HRID 2382098Notes

Reaction equation

HRID 2382098 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[Cl:8].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[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[Cl:8])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 90495Di-tert-butyl dicarbonateHCID 5819323-Amino-4-chloropyridineHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 51063702tert-Butyl (4-chloropyridin-3-yl)carbamateYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 3-amino-4-chloropyridine (6.56 g, 51 mmol) in THF (46 mL) is added 2 M NaHMDS in THF (50 mL, 100 mmol). After stirring at rt for 15 min BOC2O (10.1 g, 46.4 mmol) in THF (26 mL) is added in one portion and the mixture is stirred for 3 h at rt. 0.1% aqueous HCl (590 mL) is added. The mixture is extracted with EtOAc. The organic layer is dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel chromatography eluting with 0-50% EtOAc in heptane to afford (4-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (6.78 g, 76%). MS: 229 (M+H); 1H NMR (300 MHz, CDCl3): δ 9.38 (ms 1H), 8.23 (d, 1H), 7.30 (dd, 1H), 6.85 (broad s, 1H), 1.57 (s, 9H).

Workup

  1. additionis added in one portion
  2. extractionThe mixture is extracted with EtOAc
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by silica gel chromatography
  7. washeluting with 0-50% EtOAc in heptane

Sources & evidence

ORD record
ord-3e8d565f72b94ad3928e708652381850
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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