Methyl chloroformate → HCID 131723425, compound

HRID 2302275Notes

Reaction equation

HRID 2302275 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.ClC(OC)=O.[NH2:28][CH:29]1[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[C:33](=[O:40])[N:32]([CH:41]([CH3:43])[CH3:42])[N:31]([CH3:44])[C:30]1=[O:45]>ClCCl>[CH3:44][N:31]1[C:30](=[O:45])[CH:29]([NH:28][C:13](=[O:15])[C@@H:9]([NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH:10]([CH3:11])[CH3:12])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[C:33](=[O:40])[N:32]1[CH:41]([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 79724-MethylmorpholineHCID 83693Boc-L-ValineHCID 12015734HCID 12015734, compound

Product 1

HCID 131723425HCID 131723425, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-boc-(L)-valine (IV, 1.04 g, 4.8 mmol) in dichloromethane (100 mL) was added the N-methyl morpholine (0.56 g, 5.6 mmol) and methyl chloroformate (0.37 mL, 4.8 mmol) at 0° C. The resulting solution was stirred for 10 minutes before the addition of a solution of 5(R,S)-amino-2,3,4,5-tetrahydro-3-methyl-2-(1-methylethyl)-1H-2,3-benzodiazepin-1,4-dione (IIIA, 1.0 g, 4.04 mmol) in dichloromethane (5 mL) and it was further stirred for another 1 h. The resulting mixture was washed with 1N hydrochloric acid (50 mL), sodium bicarbonate (50 mL), brine (50 mL) and dried over MgSO4, filtered and concentrated to afford the crude product. This product was purified further on flash (silica gel) chromatography (hexane/ethyl acetate, 3/2) to afford 2,3,4,5-tetrahydro-3-methyl-5(R,S)-[[(2S)-2-[(1,1-dimethylethoxycarbonyl)amino]-3-methyl-1-oxobutyl]amino]-2-(1-methylethyl)-1H-2,3-benzodiazepin-1,4-dione(1.5 g, 83%).

Workup

  1. washThe resulting mixture was washed with 1N hydrochloric acid (50 mL), sodium bicarbonate (50 mL), brine (50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto afford the crude product
  6. customThis product was purified further on flash (silica gel) chromatography (hexane/ethyl acetate, 3/2)

Sources & evidence

ORD record
ord-0d97ae02b9674d62bc01ab76d686aad9
Source dataset
uspto-grants-2002_08
Patent number
US06432944B1

Reaction notes

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