Hydrochloric Acid → (3RS)-3-amino-1-ethoxycarbonylmethyl-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one

HRID 963463Notes

Reaction equation

HRID 963463 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])=[N:10][CH:9]([NH:25]C(OC(C)(C)C)=O)[C:8]1=[O:33])=[O:5])[CH3:2].Cl.O.C(=O)(O)[O-].[Na+]>CO.C(OCC)(=O)C>[NH2:25][CH:9]1[N:10]=[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:7]([CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5])[C:8]1=[O:33]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 516892Sodium BicarbonateHCID 19081166(3RS)-1-ethoxycarbonylmethyl-3-tert-butoxycarbonylamino-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one

Product 1

HCID 10066773(3RS)-3-amino-1-ethoxycarbonylmethyl-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-oneYield 97.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3RS)-1-ethoxycarbonylmethyl-3-tert-butoxycarbonylamino-5-(2-fluorophenyl)-2,3-dihydro-1H -1,4-benzo-diazepin-2-one (7.2 g) in methanol (100 ml) was added 4N solution of hydrogen chloride in ethyl acetate (55 ml) under stirring at ambient temperature. The mixture was stirred for 4 hours under the same condition and allowed to stand overnight. The solvent was removed in vacuo to give residue, to which was added water. The mixture was adjusted to pH 8 with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate twice. The combined extract was washed with water and dried over magnesium sulfate. Removal of the solvent afford (3RS)-3-amino-1-ethoxycarbonylmethyl-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one (5.46 g) as an amorphous mass, which was used in a following reaction step without further purification,

Workup

  1. stirringThe mixture was stirred for 4 hours under the same condition
  2. customThe solvent was removed in vacuo
  3. customto give residue
  4. extractionextracted with ethyl acetate twice
  5. extractionThe combined extract
  6. washwas washed with water
  7. dry with materialdried over magnesium sulfate
  8. customRemoval of the solvent

Sources & evidence

ORD record
ord-329f5d76fda342d5be24e743c8f94397
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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