Sodium Hydroxide → HCID 16727128, compound

HRID 1976983Notes

Reaction equation

HRID 1976983 reaction equation
C[O:2][C:3](=[O:34])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([C:26]2[C:31]([Cl:32])=[CH:30][CH:29]=[CH:28][C:27]=2[Cl:33])=[O:25])=[CH:19][CH:18]=1)[NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:15])=[O:7].[OH-].[Na+]>C(O)C>[Cl:32][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:33])[C:26]=1[C:24]([NH:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C@@H:4]([C:3]([OH:34])=[O:2])[NH:5][C:6]([C:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=2[Cl:15])=[O:7])=[CH:22][CH:21]=1)=[O:25]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 11489264HCID 11489264, compound

Product 1

HCID 16727128HCID 16727128, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
42.5 °C

Procedure

To a suspension of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[(2-chloro-6-methylphenyl)carbonyl]-L-phenylalanine methyl ester (166 mmol, 86.2 g) in ethanol (350 mL) was added aqueous 1.0 N sodium hydroxide (250 mL) at room temperature. The mixture was heated to 40-45° C. and the resulting clear solution was stirred for 3-4 h. Then, the mixture was cooled to room temperature and the ethanol was removed on a rotary evaporator. The residue was diluted with 100 mL of water. The neutral impurities was extracted into ether (2×100 mL) and the basic aqueous layer was neutralized with 1 N HCl. The precipitated solid was collected by filtration and the solid cake was washed with water (1 L) and dried at air over weekend. The crude solid was dissolved in hot acetontile (2 L) and the resulting solution was stored in the refrigerator for 15 h. The white crystalline solids were collected by filtration and washed with cold acetonitrile (100 mL). After air drying, 79.76 g (95%) of a white solid, mp 212-215° C. was obtained. 1H NMR, DMSO-d6 (400 MHz) δ10.66 (s, 1H), 8.85 (d, 1H, J=19 Hz), 7.47-7.6 (m, 5H), 7.15-7.29 (m, 5H), 4.58-4.68 (m, 1H), 3.12 (dd, 1H, J=17, 13 Hz), 2.87 (dd, 1H, J=17, 11 Hz), 2.09 (s, 3H). HR MS: Obs. mass, 505.0483. Calcd. mass. 505.0488 (M+).

Workup

  1. temperatureThen, the mixture was cooled to room temperature
  2. customthe ethanol was removed on a rotary evaporator
  3. additionThe residue was diluted with 100 mL of water
  4. extractionThe neutral impurities was extracted into ether (2×100 mL)
  5. filtrationThe precipitated solid was collected by filtration
  6. washthe solid cake was washed with water (1 L)
  7. customdried at air over weekend
  8. dissolutionThe crude solid was dissolved in hot acetontile (2 L)
  9. waitthe resulting solution was stored in the refrigerator for 15 h
  10. filtrationThe white crystalline solids were collected by filtration
  11. washwashed with cold acetonitrile (100 mL)
  12. customAfter air drying

Sources & evidence

ORD record
ord-c43cf239539e43f3a9321b215f06145b
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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