Acetic Acid → HCID 131723426, compound

HRID 2302277Notes

Reaction equation

HRID 2302277 reaction equation
[CH3:1][N:2]1[C:8](=[O:9])[CH2:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[CH2:4][N:3]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.C(C1C=C(C(C)C)C=C(C(C)C)C=1S([N:56]=[N+:57]=[N-:58])(=O)=O)(C)C.C(O)(=O)C>O1CCCC1.CCOC(C)=O>[N:56]([CH:7]1[C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[CH2:4][N:3]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[N:2]([CH3:1])[C:8]1=[O:9])=[N+:57]=[N-:58]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 1140TolueneHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 86758394HCID 86758394, compound

Product 1

HCID 131723426HCID 131723426, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a well stirred solution of 2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester (1.0 g, 3.62 mmol) in anhydrous tetrahydrofuran (30 mL) at −78° C. was added a solution of 0.5 M potassium bis(trimethylsilyl)amide in toluene (9.0 mL, 4.5 mmol). The reaction mixture was stirred for another 15 min followed by addition of a pre-cooled solution (−78° C.) of 2,4,6-triisopropylbenzenesulfonyl azide (trisyl azide) (1.23 g, 4.0 mmol) in THF (0.4M) via a cannula over a period of 1 min (Evans, et al., J. Amer. Chem. Soc., 1990, 112, 4011-4030; Butcher, et al., Tetrahedron Lett., 1996, 37 (37), 6685-6688). After 5 min, acetic acid (1.0 mL, 18 mmol) was added and stirring continued for another 6 h. The reaction mixture was diluted with EtOAc (300 mL), washed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL). The solvent was removed and the 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester was purified by flash chromatography (silica) using 10% EtOAc in hexane. The azide was obtained in 60% yield.

Workup

  1. waitAfter 5 min
  2. stirringstirring
  3. waitcontinued for another 6 h
  4. washwashed with water (300 mL), aqueous NaHCO3 (2×150 mL), 0.5 N HCl (200 mL) and brine (150 mL)
  5. customThe solvent was removed
  6. customthe 5(R,S)-azido-2,3,4,5-tetrahydro-3-methyl-4-oxo-1H-2,3-benzodiazepine-2-carboxylic acid, 1,1-dimethylethyl ester was purified by flash chromatography (silica)

Sources & evidence

ORD record
ord-e9d32510a3964d63aebe46d5f431a09d
Source dataset
uspto-grants-2002_08
Patent number
US06432944B1

Reaction notes

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