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

HRID 2229949Notes

Reaction equation

HRID 2229949 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:15][C:16]([NH:18][CH:19]1[C:25](=[O:26])[NH:24][C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[NH:21][CH2:20]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].Br[CH2:32][C:33]([O:35][CH3:36])=[O:34]>C1COCC1.C(OCC)(=O)C>[CH3:36][O:35][C:33](=[O:34])[CH2:32][N:24]1[C:25](=[O:26])[C@@H:19]([NH:18][C:16]([O:15][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:17])[CH2:20][NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[CH:27][C:23]1=2

Participants

6

Reactant 3

HCID 60984Methyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 15490831HCID 15490831, compound

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 3-tert-butoxycarbonylamino-1,3,4,5-tetrahydrobenzo[b][1,4]diazepin-2-one (0.94 g, 3.38 mmol) in 20 ml of anhydrous tetrahydrofuran and stirred for 30 minutes. Methyl bromoacetate (o0.44 ml, 4 mmol) was added dropwise to the reaction mixture then warmed to room temperature. The reaction was diluted with 100 ml of ethyl acetate and washed with 0.3N potassium hydrogen sulfate (50 ml), water (2×50 ml), and brine. The combined organics were dried over anhydrous sodium sulfate, filtered, and evaporated to afford a gum that was purified by flash chromatography eluting with 3:7 EtOAc/Hex. to give 0.98 g (83%) of the title compound as a white solid. 1H NMR (CDCl3) δ7.15-7.07 (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 potassium hydrogen sulfate (50 ml), water (2×50 ml), and brine
  2. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customto afford a gum that
  6. customwas purified by flash chromatography
  7. washeluting with 3:7 EtOAc/Hex

Sources & evidence

ORD record
ord-8bf1949fb0874cb9a178ba6d08fca121
Source dataset
uspto-grants-2002_07
Patent number
US06420522B1

Reaction notes

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