Sodium Iodide → [(S)-1-(6-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 1481894Notes

Reaction equation

HRID 1481894 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.[Br:31][C:32]1[CH:33]=[C:34]2[C:39](=[CH:40][CH:41]=1)[C:38]([CH2:42]Cl)=[C:37]([O:44][CH3:45])[CH:36]=[CH:35]2.[Na+].[I-]>C1COCC1>[C:1]([O:5][C:6](=[O:20])[NH:7][C@@H:8]1[C:14](=[O:15])[N:13]([CH2:42][C:38]2[C:39]3[C:34](=[CH:33][C:32]([Br:31])=[CH:41][CH:40]=3)[CH:35]=[CH:36][C:37]=2[O:44][CH3:45])[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 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 2733832Lithium HexamethyldisilazideHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate2×

Product 1

HCID 72713836[(S)-1-(6-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 72.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 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) (6.5 g, 23.48 mmol) in THF (100 mL) at −78° C. was added 1 M LiHMDS (4.7 g, 28 mL, 28 mmol). The cooling bath was removed and the mixture stirred at RT for 1 h. The mixture was cooled to −78° C. and a mixture of 6-bromo-1-chloromethyl-2-methoxy-naphthalene (8.0 g, 28.12 mmol) and NaI (4.2 g, 28.12 mmol) in dry THF (30 mL) was added dropwise. The cooling bath was removed and the mixture stirred at RT for 18 h. The mixture was diluted with saturated NH4Cl, extracted with ethyl acetate and the organic layer washed with water, brine, dried (Na2SO4) and concentrated to give a material which was purified by silica gel chromatography to afford the title compound (9 g, 72%) as a yellow solid. LC-MS: 528.0 (M+H).

Workup

  1. customThe cooling bath was removed
  2. temperatureThe mixture was cooled to −78° C.
  3. additionwas added dropwise
  4. customThe cooling bath was removed
  5. stirringthe mixture stirred at RT for 18 h
  6. additionThe mixture was diluted with saturated NH4Cl
  7. extractionextracted with ethyl acetate
  8. washthe organic layer washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give a material which
  12. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-e7f62fef4e4644f281f37e7a031c19bf
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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