2-Amino-5-nitrobenzophenone → (9H-fluoren-9-yl)methyl 1-(2-benzoyl-4-nitrophenylamino)-1-oxopropan-2-ylcarbamate

HRID 2188598Notes

Reaction equation

HRID 2188598 reaction equation
[C:1]([NH:18][C@H:19]([C:21](O)=[O:22])[CH3:20])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].O=S(Cl)Cl.[NH2:28][C:29]1[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][C:30]=1[C:31]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:32].C([O-])(O)=O.[Na+]>C(O)C.C(Cl)(Cl)Cl>[C:31]([C:30]1[CH:39]=[C:40]([N+:43]([O-:45])=[O:44])[CH:41]=[CH:42][C:29]=1[NH:28][C:21](=[O:22])[CH:19]([NH:18][C:1](=[O:2])[O:3][CH2:4][CH:5]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=2[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:20])(=[O:32])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 156812-Amino-5-nitrobenzophenoneHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 6364642N-((9H-Fluoren-9-ylmethoxy)carbonyl)-L-alanine

Product 1

HCID 68444468(9H-fluoren-9-yl)methyl 1-(2-benzoyl-4-nitrophenylamino)-1-oxopropan-2-ylcarbamateYield 98%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

Commercially-available (S)-Fmoc-alanine (2.98 g, 0.96 mmol) was suspended in ethanol-free CHCl3 (30 mL) and SOCl2 (7 mL) was added under N2. The mixture was heated at 50° C. for 1 h, then the solvent was removed under vacuum, the residue was dissolved into CHCl3 (30 mL), commercially-available 2-amino-5-nitro-benzophenone (2.32 g, 0.96 mmol) was added, and the mixture was heated for 2 h at 60° C. After cooling, a saturated solution of NaHCO3 was added, the organic phase was collected and dried (Na2SO4), then the solvent was removed under vacuum obtaining (9H-fluoren-9-yl)methyl 1-(2-benzoyl-4-nitrophenylamino)-1-oxopropan-2-ylcarbamate (98% yield). This compound was dissolved in CH2Cl2 (40 mL), Et3N (10 mL) was added and the mixture was heated at 40° C. for 30 h under N2. The solvent was removed under vacuum and the residue was partitioned between 2N HCl and ethyl acetate; the aqueous layer was made alkaline with 10% NaOH and extracted with CH2Cl2. After drying (Na2SO4) and removal of solvent, the residue was purified by flash chromatography (cyclohexane/ethyl acetate 6:4 as eluent) yielding (S)-3-methyl-7-nitro-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one in 25% yield.

Workup

  1. customthe solvent was removed under vacuum
  2. additionwas added
  3. temperaturethe mixture was heated for 2 h at 60° C
  4. temperatureAfter cooling
  5. customthe organic phase was collected
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-7fb0737cfb174bba88ac1c27e2f396b2
Source dataset
uspto-grants-2012_12
Patent number
US08324202B2

Reaction notes

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