Methyl bromoacetate → (3S)-2-Oxo-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-acetic acid methyl ester

HRID 1384716Notes

Reaction equation

HRID 1384716 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:11]=[C:12]1[NH:18][C:17]2[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=2[NH:15][CH2:14][C@@H:13]1[NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].Br[CH2:32][C:33]([O:35][CH3:36])=[O:34]>C1COCC1.CCOC(C)=O>[CH3:36][O:35][C:33](=[O:34])[CH2:32][N:18]1[C:17]2[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=2[NH:15][CH2:14][C@H:13]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:12]1=[O:11]

Participants

6

Reactant 3

HCID 60984Methyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 22881971tert-butyl N-[(3S)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]carbamate

Product 1

HCID 54305289(3S)-2-Oxo-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-acetic acid methyl esterYield 83%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 1.0 M solution of lithium bis(trimethylsilyl)amide (3.4 ml, 3.4 mmol) in THF was added dropwise to a −78° C. solution of (3S)-2-oxo-3-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.94 g, 3.38 mmol) in 20 ml of anhydrous THF and stirred for 30 min. Methyl bromoacetate (0.44 ml, 4 mmol) was added dropwise to the reaction mixture then warmed to RT. The reaction was diluted with 100 ml of EtOAc and washed with 0.3N KHSO4 (50 ml), H2O (2×50 ml), and brine. The combined organics were dried over anhydrous Na2SO4, filtered, and evaporated to afforded a gum that was purified by flash chromatography eluzing with 3:7 EtOAc/Hex. to give 0.98 g (83%) of the title compound as a white solid. 1H NMR (CDCl3) δ 7.15-7.07 (2H, m), 6.98-6.94 (1H, m), 6.88-6.84 (1H, d), 5.62-5.55 (1H, d), 4.71-4.65 (1H, d), 4.65-4.6 (1H, m), 4.33-4.27 (1H, d), 3.96-3.90 (1H, m), 3.78 (3H, s), 3.44-3.37 (1H, m), 1.4 (9H, s).

Workup

  1. washwashed with 0.3N KHSO4 (50 ml), H2O (2×50 ml), and brine
  2. dry with materialThe combined organics were dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afforded a gum that
  6. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-3992232569d946d195d6803310c9b7c7
Source dataset
uspto-grants-2001_07
Patent number
US06258948B1

Reaction notes

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