Hydrochloric Acid → HCID 68604115, compound

HRID 2267637Notes

Reaction equation

HRID 2267637 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:17][C@@H:18]2[C:24](=[O:25])[N:23]([CH2:26][C:27]([O:29]C)=[O:28])[C:22]3[CH:31]=[CH:32][CH:33]=[CH:34][C:21]=3[O:20][C@@H:19]2[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:16])[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[OH-].[Li+].CO.Cl>C1COCC1.O>[F:8][C:6]1[CH:5]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:17][C@@H:18]2[C:24](=[O:25])[N:23]([CH2:26][C:27]([OH:29])=[O:28])[C:22]3[CH:31]=[CH:32][CH:33]=[CH:34][C:21]=3[O:20][C@@H:19]2[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:16])[CH3:14])=[O:11])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 86604639HCID 86604639, compound

Product 1

HCID 68604115HCID 68604115, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of methyl [(2R,3S)-3-({N-[(3,5-difluorophenyl)acetyl]-L-alanyl}amino)-4-oxo-2-phenyl-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]acetate (70) (133 mg, 0.241 mmol) in THF (4 mL) was added a solution of lithium hydroxide (11 mg, 0.262 mmol) in water (1 mL). Several small drops of methanol were then added until a clear homogeneous solution was achieved. The mixture was stirred for 1 h at ambient temperature then acidified with 1N aqueous HCl and extracted with ethyl acetate. The organic solution was dried, filtered and evaporated. The glass-like solid residue was dissolved in dichloromethane (2 mL) then precipitated by addition of hexanes to afford the title compound (124 mg, 96%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ1.08 (d, 3H, J=7.0 Hz), 3.41 and 3.48 (AB quartet, 2H, J=14.5 Hz), 4.21 (m, 1H), 4.58 (s, 2H), 5.02 (t, 1H, J=7.0 Hz), 5.55 (d, 1H, J=7.0 Hz), 6.94 (m, 2H), 7.08 (m, 1H), 7.24-7.49 (m, 10H), 8.33 (d, 1H, J=7.0 Hz), 12.94 (br, 1H). MS APCI, m/z=538 (M+1). LC/MS: 2.27 min.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic solution was dried
  3. filtrationfiltered
  4. customevaporated
  5. dissolutionThe glass-like solid residue was dissolved in dichloromethane (2 mL)
  6. customthen precipitated by addition of hexanes

Sources & evidence

ORD record
ord-770f2b81f85d4cec93f479b41f2c5a44
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

Loading…