acetyl (2S)-2-hydroxy-2-phenylacetate → HCID 131733522, compound

HRID 2283418Notes

Reaction equation

HRID 2283418 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([C:10]2[C:11]([F:27])=[C:12]([C@H:17]([NH:20][CH:21]([CH3:26])[CH2:22][C:23]([NH2:25])=[O:24])[CH2:18][CH3:19])[CH:13]=[CH:14][C:15]=2[Cl:16])=[O:9])=[CH:4][CH:3]=1.[C:28]([O:31][C:32](=[O:41])[C@H:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[OH:34])(=[O:30])[CH3:29]>CCO>[C:28]([O:31][C:32](=[O:41])[C@H:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[OH:34])(=[O:30])[CH3:29].[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([C:10]2[C:11]([F:27])=[C:12]([C@H:17]([NH:20][C@@H:21]([CH3:26])[CH2:22][C:23]([NH2:25])=[O:24])[CH2:18][CH3:19])[CH:13]=[CH:14][C:15]=2[Cl:16])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 87431886acetyl (2S)-2-hydroxy-2-phenylacetateHCID 89544713HCID 89544713, compound

Product 1

HCID 131733522HCID 131733522, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Step 11—To a stirred solution of 3-{[(1R)-1-[3-(6-aminopyridine-3-carbonyl)-4-chloro-2-fluorophenyl]propyl]-amino}butanamide (237 g, 603 mmol) in EtOH (1900 mL) at 78° C. was added (+)-O-acetyl-L-mandelic acid (117 g, 603 mmol). The mixture was kept at 78° C. for 10 minutes then allowed to cool to room temperature (with stirring) providing a precipitate. After stirring overnight the solid was collected by filtration, washed with EtOH (1.25 Vol), then Et2O (1.7 Vol) and dried at 40° C. under vacuum providing (3S)-3-{[(1R)-1-[3-(6-aminopyridine-3-carbonyl)-4-chloro-2-fluorophenyl]propyl]-amino}butanamide (+)-O-acetyl-L-mandelic acid salt (206 g) diastereomer ratio of 97.5:2.5 in favour of the desired diastereomer. 1H NMR (400 MHz, DMSO-d6): 8.15 (1H, d), 7.78 (1H, dd), 7.64 (1H, t), 7.52-7.37 (6H, m), 7.31 (3H, d), 6.79 (1H, s), 6.54 (1H, d), 5.83-5.73 (1H, m), 4.01 (1H, t), 2.87-2.69 (1H, m), 2.62-2.52 (1H, m), 2.22-2.01 (2H, m), 2.12 (3H, s), 1.81-1.66 (1H, m), 1.66-1.50 (1H, m), 0.95 (3H, d), 0.78 (3H, t).

Workup

  1. customproviding a precipitate
  2. stirringAfter stirring overnight the solid
  3. filtrationwas collected by filtration
  4. washwashed with EtOH (1.25 Vol)
  5. dry with materialEt2O (1.7 Vol) and dried at 40° C. under vacuum

Sources & evidence

ORD record
ord-6c5a59e1370242eab28dfabcd0c5cd85
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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