Trifluoroacetic acid → (S)-4-Benzyloxy-2-[4-(3,4-dichloro-phenyl)-3-methyl-7-oxo-[1,4]diazepan-1-yl]-butyric Acid methyl ester

HRID 1096266Notes

Reaction equation

HRID 1096266 reaction equation
[CH3:1][O:2][C:3](=[O:36])[C@@H:4]([N:15]([CH2:24][CH:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[CH3:26])[C:16](=[O:23])[CH2:17][CH:18](OC)OC)[CH2:5][CH2:6][O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(N(CC)CC)C>C(Cl)Cl.C(OCC)C.O>[CH3:1][O:2][C:3](=[O:36])[C@@H:4]([N:15]1[C:16](=[O:23])[CH2:17][CH2:18][N:27]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)[CH:25]([CH3:26])[CH2:24]1)[CH2:5][CH2:6][O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 66782917(S)-4-Benzyloxy-2-[[2-(3,4-dichloro-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric Acid methyl ester

Product 1

HCID 66782967(S)-4-Benzyloxy-2-[4-(3,4-dichloro-phenyl)-3-methyl-7-oxo-[1,4]diazepan-1-yl]-butyric Acid methyl esterYield 51%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A cooled solution (0° C.) of 1.75 g (3.23 mmol) of (S)-4-benzyloxy-2-[[2-(3,4-dichloro-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric acid methyl ester in 30 ml CH2Cl2 was treated with 3.71 ml (48.48 mmol) of trifluoroacetic acid and after 2 h at RT with 2.57 ml (16.16 mmol) of triethylsilane. The reaction was stirred at RT for 16 h, cooled (0° C.) and neutralized with 6.76 ml (48.48 mmol) of triethylamine. The residue was dissolved in diethyl ether and cold water. The reaction was extracted with 10% aq. KHSO4 solution/diethyl ether (3×). The organic phases were washed with sat. aq. NaHCO3 solution, dried over Na2SO4 and evaporated. Flash silica gel column (n-heptane/EtOAc 4:1→1:1) afforded 0.79 g (46%) of the title compound as a 71:29 mixture of the (R) and (S) diastereomers. Orange oil, MS: 479.1 (MH+, 2Cl).

Workup

  1. temperaturecooled (0° C.)
  2. extractionThe reaction was extracted with 10% aq. KHSO4 solution/diethyl ether (3×)
  3. washThe organic phases were washed with sat. aq. NaHCO3 solution
  4. dry with materialdried over Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-dc894235e80043bb81fabeb4f302ebcb
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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