Water → 1035662-71-5

HRID 1678098Notes

Reaction equation

HRID 1678098 reaction equation
O.[Cl:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][C:41]=1[Cl:42])[CH2:6][C@@H:7]([N:21]([CH3:38])[C:22](=[O:37])[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1)/[CH:8]=[CH:9]/[C:10](=[O:20])[NH:11][C@@H:12]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:13]1=[O:19]>CO>[OH2:19].[Cl:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][C:41]=1[Cl:42])[CH2:6][C@@H:7]([N:21]([CH3:38])[C:22](=[O:37])[C:23]1[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[C:25]([C:33]([F:34])([F:35])[F:36])[CH:24]=1)/[CH:8]=[CH:9]/[C:10](=[O:20])[NH:11][C@@H:12]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:13]1=[O:19].[Cl:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][C:41]=1[Cl:42])[CH2:6][C@@H:7]([N:21]([CH3:38])[C:22](=[O:37])[C:23]1[CH:28]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:26]=[C:25]([C:33]([F:34])([F:35])[F:36])[CH:24]=1)/[CH:8]=[CH:9]/[C:10](=[O:20])[NH:11][C@@H:12]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:13]1=[O:19]

Participants

4

Reactant 2

HCID 962Water2×HCID 9939040398507-81-8

Product 1

HCID 729419741035662-71-5Yield 85.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Water (2.6 ml) is added to the stirred solution (10.5 ml) of N-[(E)-(R)-1-(3,4-dichloro-benzyl)-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (12) in methanol at approx. 18-22° C., whereupon crystallisation begins. After stirring for approx. 10 minutes, water (1 ml) is added at 18-22° C. over a period of approx. 20 minutes. Stirring at 18-22° C. is continued for 2 hours. The precipitated solids are isolated by filtration and the filter cake is rinsed with a mixture of methanol and water (2 ml+1 ml), followed by water (3 ml). The solids are dried at 30° C. in vacuo to constant weight to yield N-[(E)-(R)-1-(3,4-dichloro-benzyl)-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide hemihydrate (13) [1.6241b=85.5% of theory based on (E)-(R)-5-(3,4-dichloro-phenyl)-4-methylamino-pent-2-enoic acid ((R)-2-oxo-azepan-3-yl)-amide (10)], m.p. 127-131° C., sintering >123° C., MS-ES+: (MH)+=624 (35Cl2), [α]D20=+40.6° (methanol).

Workup

  1. stirringStirring at 18-22° C.
  2. waitis continued for 2 hours
  3. customThe precipitated solids are isolated by filtration
  4. washthe filter cake is rinsed with a mixture of methanol and water (2 ml+1 ml)
  5. customThe solids are dried at 30° C. in vacuo to constant weight

Sources & evidence

ORD record
ord-ca4152e4752e48ecbe38c329d0b4058a
Source dataset
uspto-grants-2011_08
Patent number
US08008479B2

Reaction notes

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