Methanol → HCID 178463218, compound

HRID 1373208Notes

Reaction equation

HRID 1373208 reaction equation
C(#N)C.[F:4][C:5]1[CH:41]=[CH:40][C:8]([CH2:9][CH2:10][NH:11][C:12](=[N:14][C:15]2[CH:23]=[C:22]3[C:18]([CH2:19][C@@H:20]([OH:39])[C@@H:21]3[NH:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:29][CH:28]=3)=[O:26])=[CH:17][CH:16]=2)[CH3:13])=[CH:7][CH:6]=1.CO>>[OH2:26].[F:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][CH2:10][NH:11][C:12](=[N:14][C:15]2[CH:23]=[C:22]3[C:18]([CH2:19][C@@H:20]([OH:39])[C@@H:21]3[NH:24][C:25]([C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:29][CH:28]=3)=[O:26])=[CH:17][CH:16]=2)[CH3:13])=[CH:40][CH:41]=1.[C:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:29]=[CH:28][C:27]([C:25]([NH:24][C@@H:21]2[C:22]3[C:18](=[CH:17][CH:16]=[C:15]([N:14]=[C:12]([NH:11][CH2:10][CH2:9][C:8]4[CH:40]=[CH:41][C:5]([F:4])=[CH:6][CH:7]=4)[CH3:13])[CH:23]=3)[CH2:19][C@H:20]2[OH:39])=[O:26])=[CH:32][CH:31]=1

Participants

3

Reactant 2

HCID 887MethanolHCID 178464399HCID 178464399, compound

Product 1

HCID 178463218HCID 178463218, compoundYield 122%

Procedure

Add 21.8 L of methanol to 2.86 kg of biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide acetonitrile solvate. Pass the solution through a carbon impregnated filter and rinse the filter with 24 L of methanol. Add 5.7 kg of water to the solution over 35 min followed by 15 g of biphenyl-4-carboxylic acid (R)-(6-(1-((4-fluorobenzyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide hemihydrate seed crystals. After 20 min, add 1.15 kg of water followed by 15 g of seed crystals. After 1 h, add another 1.15 kg of water over 30 min followed by 15 g of seed crystals. After 10 min, add 3.4 kg of water over 1 h and stir the slurry at room temperature for 1 h and at 0° C. for 45 min. Collect the solid by filtration, rinse with a cold solution of 11.4 L of methanol and 2.9 L of water, and dry to afford 2.19 kg of the title compound as a white solid.

Workup

  1. filtrationPass the solution through a carbon impregnated filter
  2. washrinse the
  3. filtrationfilter with 24 L of methanol
  4. additionAdd 5.7 kg of water to the solution over 35 min
  5. additionadd 1.15 kg of water
  6. waitAfter 1 h
  7. additionadd another 1.15 kg of water over 30 min
  8. waitAfter 10 min
  9. additionadd 3.4 kg of water over 1 h
  10. waitat 0° C. for 45 min
  11. customCollect the solid
  12. filtrationby filtration
  13. washrinse with a cold solution of 11.4 L of methanol and 2.9 L of water
  14. customdry

Sources & evidence

ORD record
ord-3a1dec2f5bc946dba2c3662a3f9e0cff
Source dataset
uspto-grants-2007_01
Patent number
US07160922B2

Reaction notes

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