Ethyl oxoacetate → HCID 117610997, compound

HRID 588882Notes

Reaction equation

HRID 588882 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[C:5]([Cl:11])=[CH:4][C:3]=1[OH:12].[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=O.C([BH3-])#N.[Na+]>CO.CC(O)=O>[Cl:11][C:5]1[C:6]([CH:8]2[CH2:10][CH2:9]2)=[CH:7][C:2]([NH:1][CH2:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])=[C:3]([OH:12])[CH:4]=1

Participants

6

Reactant 3

HCID 70211Ethyl oxoacetateHCID 5003444Sodium cyanoborohydrideHCID 117607191HCID 117607191, compound

Product 1

HCID 117610997HCID 117610997, compoundYield 106.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of 2-amino-5-chloro-4-cyclopropylphenol (200 mg, 1.01 mmol) in MeOH (20 mL) at RT, AcOH (3 drops) and ethyl glyoxalate (416 mg, 2.02 mmol, 50% in toluene) were added. The mixture was stirred at RT for 2 h and then sodium cyanoborohydride (190 mg, 3.03 mmol) was added to the mixture. The resulting mixture was stirred at 40° C. for 15 h. The mixture was allowed to cool to RT and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (10-20% methanol/dichloromethane) to afford the desired product (290 mg, 100% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) δ: 9.63 (s, 1H), 6.66 (s, 1H), 5.93 (s, 1H), 5.07 (t, J=6.4 Hz, 1H), 4.12 (q, J=7.2 Hz, 2H), 3.91 (d, J=6.4 Hz, 2H), 1.92-1.97 (m, 1H), 1.20 (t, J=6.8 Hz, 2H), 0.84-0.87 (m, 2H), 0.51-0.55 (m, 2H).

Workup

  1. stirringThe resulting mixture was stirred at 40° C. for 15 h
  2. temperatureto cool to RT
  3. custompartitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (10-20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-da9e0602fdf14718a5c89fe597a08952
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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