Water → HCID 18797717, compound

HRID 1003605Notes

Reaction equation

HRID 1003605 reaction equation
Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH2:4][C:5]([OH:7])=[O:6].[CH2:18](N(CC)CC)C.Cl.[C:26](Cl)(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][CH:28]=1.O>O1CCCC1>[C:26]([NH:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH2:4][C:5]([O:7][CH3:18])=[O:6])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][CH:28]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 69601897HCID 69601897, compound

Product 1

HCID 18797717HCID 18797717, compoundYield 22.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) stirred suspension of 3-amino-3-(3',4'-dimethoxyphenyl)propionate hydrochloride (1.38 grams, 5.0 mmol) and triethylamine (1.5 milliliters , 10.8 mmol) in 20 milliliters of tetrahydrofuran was added nicotinoyl chloride hydrochloride (0.89 grams, 5.0 mmol). The thick slurry was stirred for 15 minutes and then allowed to warm to room temperature and stirring was continued for 2 hours. The reaction mixture was treated with 20 milliliters of water resulting in a brown colored solution. The tetrahydrofuran was removed in vacuo and the aqueous layer was extracted with methylene chloride (3 times, milliliters). The combined extracts were dried over magnesium sulfate and concentrated in vacuo to afford an oil which solidified overnight. The white solid was dried in vacuo (60° C., <1 mm) to afford 0.52 grams (30%) of crude product. The crude product was purified by flash chromatography (silica gel, 5% methanol/methylene chloride) and dried in vacuo (60° C., <1 mm) to afford 0.38 grams (22%) of the product as a white solid: 1H NMR (CDCl3) δ 9.10-9.00(m , 1 H), 8.80-8.69(m , 1 H), 8.19-8.08(m , 1 H), 7.65-7.31(m, 2 H), 6.96-6.76(m, 3 H), 5.64-5.50(m, 1 H), 3.87(s, 3 H), 3.67(s, 3 H), 3.14-2.37(m, 2 H). 13C NMR (CDCl3) δ 6 172.1, 164.6, 152.4, 149.2, 148.7, 148.1, 135.0, 132.8, 129.9, 123.5, 118.1, 111.3, 111.2, 109.9, 109.8, 55.9, 52.0, 49.8, 39.5. HPLC 99.47%.

Workup

  1. stirringThe thick slurry was stirred for 15 minutes
  2. temperatureto warm to room temperature
  3. stirringstirring
  4. customThe tetrahydrofuran was removed in vacuo
  5. extractionthe aqueous layer was extracted with methylene chloride (3 times, milliliters)
  6. dry with materialThe combined extracts were dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customto afford an oil which
  9. waitsolidified overnight
  10. customThe white solid was dried in vacuo (60° C., <1 mm)
  11. customto afford 0.52 grams (30%) of crude product
  12. customThe crude product was purified by flash chromatography (silica gel, 5% methanol/methylene chloride)
  13. customdried in vacuo (60° C., <1 mm)

Sources & evidence

ORD record
ord-930b7562b7c7448591317d84f6f0cae7
Source dataset
uspto-grants-2000_04
Patent number
US06046221

Reaction notes

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