Benzyl chloroformate → Benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinate

HRID 1481789Notes

Reaction equation

HRID 1481789 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=[C:11]([Cl:23])[C:10]=1[CH2:24][CH3:25])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.Cl[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]>C1COCC1>[CH2:16]([O:15][C:13]1[N:12]=[C:11]([Cl:23])[C:10]([CH2:24][CH3:25])=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:14]=1[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 894217684,6-Bis(benzyloxy)-2-chloro-3-ethylpyridineHCID 178418339Butyllithium

Product 1

HCID 86280413Benzyl 2,4-bis(benzyloxy)-6-chloro-5-ethylnicotinateYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the intermediate obtained in Step 2 (7.7 g, 21.8 mmol) in THF (80 mL), at −78° C. was added n-BuLi (21.8 mL, 54.4 mmol) dropwise, and stirred for additional 15 min. at −78° C. after the addition. Benzyl chloroformate (4.7 mL, 32.6 mmol) was then added and the resulting mixture was stirred for 10 min before the cooling bath was removed. The mixture was allowed to warm to room temperature while stirring. The reaction was quenched with a solution of NH4Cl (5 mL), diluted with ethyl ether (150 mL), washed with water (2×30 mL) and brine (30 mL). After drying with Na2SO4, the solvent was removed and the residue was chromatographed (silica gel, ethylacetate in hexanes, 0-5%) to provide product as white crystalline material (6.9 g, yield: 65%).

Workup

  1. additionafter the addition
  2. stirringthe resulting mixture was stirred for 10 min before the cooling bath
  3. customwas removed
  4. temperatureto warm to room temperature
  5. stirringwhile stirring
  6. customThe reaction was quenched with a solution of NH4Cl (5 mL)
  7. additiondiluted with ethyl ether (150 mL)
  8. washwashed with water (2×30 mL) and brine (30 mL)
  9. dry with materialAfter drying with Na2SO4
  10. customthe solvent was removed
  11. customthe residue was chromatographed (silica gel, ethylacetate in hexanes, 0-5%)

Sources & evidence

ORD record
ord-1b7c2c8a931741feb048607b2d5e7ca8
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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