Sodium Hydroxide → Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl ester

HRID 7665Notes

Reaction equation

HRID 7665 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[CH2:13][NH:12]2)=[O:10])=[CH:4][CH:3]=1.[O:25]([C:32]1[N:37]=[C:36]([C:38](Cl)=[O:39])[CH:35]=[CH:34][N:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[OH-].[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]2[CH2:15][CH:14]([O:16][C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[CH2:13][N:12]2[C:38]([C:36]2[CH:35]=[CH:34][N:33]=[C:32]([O:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:37]=2)=[O:39])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 129701582-Phenoxypyrimidine-4-carbonyl chlorideHCID 20724737Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl ester

Product 1

HCID 20724735Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-2-(2-phenoxypyrimidine-4-carbonyl)-pyrazolidin-4-yl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl ester, 41, (354 mg, 1.05 mmol) and 2-phenoxypyrimidine-4-carbonyl chloride, 18, (345 mg, 1.47 mmol) are dissolved in dichloromethane (2 mL). 1.0 N NaOH (3 mL) is added dropwise at room temperature while vigorously stirring. The reaction is allowed to proceed for 12 hours after which time additional acid chloride, 18, is added and stirring continued for 3 hours. Additional acid chloride, 18, (83 mg) is added and stirring continued for an additional 12 hours. After which time the reaction is diluted with dichloromethane (50 mL) and washed with water (50 mL). The combined organic layers are washed with NaHCO3 (sat.) (50 mL) and brine (50 mL), dried, filtered and concentrated to provide a brown oil. The crude material is purified over silica (100% ethyl acetate to 5% methyl alcohol/ethyl acetate) afford 348 mg (61% yield) of the desired product as a viscous oil.

Workup

  1. stirringstirring
  2. waitcontinued for 3 hours
  3. stirringstirring
  4. waitcontinued for an additional 12 hours
  5. washwashed with water (50 mL)
  6. washThe combined organic layers are washed with NaHCO3 (sat.) (50 mL) and brine (50 mL)
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide a brown oil
  11. customThe crude material is purified over silica (100% ethyl acetate to 5% methyl alcohol/ethyl acetate)

Sources & evidence

ORD record
ord-7d30b541628c4d209e47355cf4b279db
Source dataset
uspto-grants-2006_08
Patent number
US07087615B2

Reaction notes

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