Sodium Iodide → [(S)-1-(5-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester

HRID 1481895Notes

Reaction equation

HRID 1481895 reaction equation
[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[I-].[Na+].[Br:33][C:34]1[CH:43]=[CH:42][CH:41]=[C:40]2[C:35]=1[CH:36]=[CH:37][C:38]([O:46][CH3:47])=[C:39]2[CH2:44]Cl>C1COCC1>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:44][C:39]2[C:40]3[C:35](=[C:34]([Br:33])[CH:43]=[CH:42][CH:41]=3)[CH:36]=[CH:37][C:38]=2[O:46][CH3:47])[C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 2733832Lithium HexamethyldisilazideHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate2×HCID 899225115-Bromo-1-(chloromethyl)-2-methoxynaphthalene

Product 1

HCID 90221057[(S)-1-(5-Bromo-2-methoxy-naphthalen-1-ylmethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl esterYield 82.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of ((S)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester (Intermediate 2) (500 mg, 1.805 mmol) in THF (10 mL) at −78° C. was added LiHMDS (1 M in THF, 2.3 mL, 2.3 mmol) dropwise over 5 min. The mixture was stirred at −78° C. for 20 min. and a mixture of sodium iodide (295.8 mg, 1.986 mmol) and 5-bromo-1-chloromethyl-2-methoxy-naphthalene (617.3 mg, 2.166 mmol) in THF (5 mL), was added dropwise over 5 min. The mixture was stirred at −78° C. for 50 min. and the cooling bath was removed. After 16 h, aqueous citric acid was added and the mixture extracted with ethyl acetate. The extract was washed with saturated sodium carbonate solution, dried and concentrated to give a material which was purified by silica gel chromatography to provide the title compound (780 mg, 82%) as a white solid. LC-MS: 528 (M+H).

Workup

  1. additionwas added dropwise over 5 min
  2. stirringThe mixture was stirred at −78° C. for 50 min.
  3. customthe cooling bath was removed
  4. waitAfter 16 h
  5. additionaqueous citric acid was added
  6. extractionthe mixture extracted with ethyl acetate
  7. washThe extract was washed with saturated sodium carbonate solution
  8. customdried
  9. concentrationconcentrated
  10. customto give a material which
  11. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-f9b145a24ab141988d4765d127445dfe
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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