Acetic Anhydride → HCID 86666224, compound

HRID 705980Notes

Reaction equation

HRID 705980 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]([CH:6]([C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=1)[OH:7])=[CH2:5].[C:16](OC(=O)C)(=[O:18])[CH3:17]>ClCCl.CN(C1C=CN=CC=1)C.C([O-])(O)=O.[Na+]>[CH3:1][O:2][C:3](=[O:15])[C:4]([CH:6]([O:7][C:16](=[O:18])[CH3:17])[C:8]1[CH:9]=[N:10][C:11]([Cl:14])=[CH:12][CH:13]=1)=[CH2:5]

Participants

6

Reactant 2

HCID 7918Acetic AnhydrideHCID 86666223HCID 86666223, compound

Product 1

HCID 86666224HCID 86666224, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[(6-chloro-pyridin-3-yl)-hydroxymethyl]acrylic acid methyl ester (4.788 mmol, 1 eq) in dichloromethane (10 ml), molecular sievies 4 Å and 4-DMAP (1.915 mmol, 0.4 eq) were added. Reaction mixture was cooled to 0° C. and acetic anhydride (7.182 mmol, 1.5 eq) was added. Mixture allowed to reach room temperature and stirred for 2 hours. The reaction mixture was poured in 50 ml NaHCO3 (sat.) and extraction with DCM (3×100 ml) followed. Organic layers were combined and evaporated to give crude product which was purified on Biotage SP1 Snap Si 25; 25 ml/min in the gradient of EtOAc in Cyclohexan: 10-45% in 15 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product 2-(acetoxy-(6-chloro-pyridin-3-yl)-methyl]-acrylic acid methyl ester (2.099 mmol, yield=44%, purity=100%). [M+H]+=270.19 1H NMR (300 MHz, CDCl3) δ/ppm 2.10 (s, 3H), 3.69 (s, 3H), 5.97 (d, J=0.9 Hz, 1H), 6.44 (s, 1H), 6.62 (s, 1H), 7.19-7.33 (m, 1H), 7.58-7.70 (m, 1H), 8.35-8.44 (m, 1H)

Workup

  1. customReaction mixture
  2. customto reach room temperature
  3. extractionextraction with DCM (3×100 ml)
  4. customevaporated
  5. customto give crude product which
  6. customwas purified on Biotage SP1 Snap Si 25
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-edbb944b55124664ab4cbb6b9ee0db3f
Source dataset
uspto-grants-2015_11
Patent number
US09174968B2

Reaction notes

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