Lithium hydroxide, monohydrate → HCID 59828862, compound

HRID 1191135Notes

Reaction equation

HRID 1191135 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8](C(=O)C(F)(F)F)[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH:28][C:29]([CH:31]2[CH2:33][CH2:32]2)=[O:30])=[CH:23][CH:22]=1.O[Li].O>CO>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:27][NH:28][C:29]([CH:31]2[CH2:32][CH2:33]2)=[O:30])=[CH:25][CH:26]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86624176HCID 86624176, compound

Product 1

HCID 59828862HCID 59828862, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve 7-chloro-6-{4-[(cyclopropanecarbonyl-amino)-methyl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (335 mg, 0.698 mmol) in MeOH (10 mL). Add LiOH.H2O (293 mg, 6.98 mmol) and stir overnight. Partition the reaction mixture between chloroform and water. Separate the aqueous phase and extract three times with chloroform and once with chloroform/iso-propanol (3:1). Dry the combined organic extracts over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g, pre-packed cartridge) eluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15; 50 mL/min) to obtain 7-chloro-6-{-4-[(cyclopropanecarbonyl-amino)-methyl]-benzylamino}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (244 mg, 91%). MS (APCI+) m/z: 384 (M+H)+.

Workup

  1. customPartition the reaction mixture between chloroform and water
  2. customSeparate the aqueous phase
  3. extractionextract three times with chloroform
  4. dry with materialDry the combined organic extracts over MgSO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude mixture by chromatography on silica gel (40 g, pre-packed cartridge)
  8. washeluting with DCM/(chloroform:methanol:concentrated NH4OH 80:18:2) (1:0 over 5 min, 19:1 over 5 min, 9:1 over 5 min, 85:15; 50 mL/min)

Sources & evidence

ORD record
ord-d1c2d15b28b14e42b9dd5c4e76a2f8cb
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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