m-Toluidine → alpha-benzyl 4-[N,N-bis(2-chloroethyl)-amino]phenoxycarbonyl-gamma-(3-methylphenyl)-L-glutamine

HRID 861219Notes

Reaction equation

HRID 861219 reaction equation
[CH2:1]([C@@:8]([C:31]([O-:33])=[O:32])([CH2:19][CH:20]([N:24]([CH2:28][CH2:29][Cl:30])[CH2:25][CH2:26][Cl:27])[C:21]([O-:23])=O)[NH:9][C:10]([O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:36](CC)CC)C.C(OC(Cl)=O)C(C)C.N[C:50]1[CH:55]=[CH:54][CH:53]=[C:52]([CH3:56])[CH:51]=1>O1CCCC1>[CH2:1]([C@@:8]([C:31]([OH:33])=[O:32])([CH2:19][C:20]([N:24]([CH2:25][CH2:26][Cl:27])[CH2:28][CH2:29][Cl:30])([C:50]1[CH:55]=[CH:54][CH:53]=[C:52]([CH3:56])[CH:51]=1)[C:21](=[O:23])[NH2:36])[NH:9][C:10]([O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 7934m-ToluidineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 86752017HCID 86752017, compound

Product 1

HCID 86752016alpha-benzyl 4-[N,N-bis(2-chloroethyl)-amino]phenoxycarbonyl-gamma-(3-methylphenyl)-L-glutamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
25 °C

Procedure

α-Benzyl4-[N,N-bis(2-chloroethyl)amino]phenoxycarbonyl-L-glutamate (300 mg) in dry tetrahydrofuran (5 ml) was treated with 1.1 equivalents of triethylamine. Isobutylchloroformate (0.08 ml, 1.1 equiv) in dry THF (10 ml) was added slowly to the reaction mixture at -25° C. After 15 minutes, 1.1 equivalents (0.08 ml) m-toluidine in dry tetrahydrofuran (5 ml) was added. The mixture was allowed to warm up to 25° C. and was then continuously stirred for 18 hrs. The reaction mixture was then filtered and the filtrate evaporated to give a residue which was purified by flash column chromatography using mixtures of ethyl acetate/hexane as eluent. Evaporation of appropriate fractions yielded α-benzyl 4-[N,N-bis(2-chloroethyl)amino]phenoxycarbonyl-γ-(3-methylphenyl)-L-glutamine as a white crystalline solid. The NMR data from this product is set out in Table 17.

Workup

  1. filtrationThe reaction mixture was then filtered
  2. customthe filtrate evaporated
  3. customto give a residue which
  4. customwas purified by flash column chromatography
  5. customEvaporation of appropriate fractions

Sources & evidence

ORD record
ord-6df02528b8f142f18b095e42036348e7
Source dataset
uspto-grants-1998_02
Patent number
US05714148

Reaction notes

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