Hydrochloric Acid → (3RS)-3-amino-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one

HRID 963470Notes

Reaction equation

HRID 963470 reaction equation
[CH:1]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH2:3][N:2]1[C:12]([CH2:14][N:15]1[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[C:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[F:32])=[N:18][CH:17]([NH:33]C(OC(C)(C)C)=O)[C:16]1=[O:41])=[O:13])[CH2:9]2.Cl>[N+](C)([O-])=O>[NH2:33][CH:17]1[N:18]=[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[N:15]([CH2:14][C:12]([N:2]2[CH2:3][CH:4]3[CH2:10][CH:8]4[CH2:7][CH:6]([CH2:11][CH:1]2[CH2:9]4)[CH2:5]3)=[O:13])[C:16]1=[O:41]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67688125(3RS)-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one

Product 1

HCID 54065770(3RS)-3-amino-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-oneYield 72.5%

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent

Procedure

To a solution of (3RS)-1-[(2-azatricyclo[4.3.1.14,8 ]-undec-2-yl) carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-di-hydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.445 g) in nitromethane was treated with hydrogen chloride under stirring at cooling in an ice-bath. The mixture was concentrated in vacuo. The residue was dissolved with ethyl acetate and extracted with 1N hydrochloric acid aqueous solution three times. The combined aqueous layers were alkalined with sodium bicarbonate, extracted with ethyl acetate twice. The extracts were dried over sodium sulfate. Removal of the solvent gave (3RS)-3-amino-1-[(2-azatricyclo[4.3.1.14,8 ]undec-2-yl)carbonylmethyl]-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.265 g), which was used in a following reaction step without further purification.

Workup

  1. temperatureat cooling in an ice-bath
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved with ethyl acetate
  4. extractionextracted with 1N hydrochloric acid aqueous solution three times
  5. extractionextracted with ethyl acetate twice
  6. dry with materialThe extracts were dried over sodium sulfate
  7. customRemoval of the solvent

Sources & evidence

ORD record
ord-9ea6530f3ac743319d3db808ae5b8a82
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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