Trifluoroacetic acid → 4-[(R)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-7-oxo-2,3,4,7-tetrahydro-[1,4]diazepin-1-yl]-butyric acid

HRID 2095507Notes

Reaction equation

HRID 2095507 reaction equation
C([O:5][C:6](=[O:34])[CH2:7][CH2:8][CH2:9][N:10]([CH2:19][C@H:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[C:25]([Cl:33])[CH:24]=1)[CH3:21])[C:11](=[O:18])[CH2:12][CH:13](OC)OC)(C)(C)C.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(N(CC)CC)C>C(Cl)Cl.C(OCC)C.O>[Cl:33][C:25]1[CH:24]=[C:23]([N:22]2[CH:13]=[CH:12][C:11](=[O:18])[N:10]([CH2:9][CH2:8][CH2:7][C:6]([OH:5])=[O:34])[CH2:19][C@H:20]2[CH3:21])[CH:28]=[CH:27][C:26]=1[C:29]([F:32])([F:30])[F:31]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 670739484-[[(R)-2-(3-Chloro-4-trifluoromethyl-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric acid tert-butyl ester

Product 1

HCID 670747854-[(R)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-7-oxo-2,3,4,7-tetrahydro-[1,4]diazepin-1-yl]-butyric acidYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A cooled solution (0° C.) of 1.00 g (2.00 mmol) of 4-[[(R)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propyl]-(3,3-dimethoxy-propionyl)-amino]-butyric acid tert-butyl ester (22% ee) in 18 ml CH2Cl2 was treated with 2.25 ml (29.40 mmol) of trifluoroacetic acid and after 2 h at RT with 1.55 ml (9.80 mmol) of triethylsilane. The reaction was stirred at RT for 16 h, cooled (0° C.) and neutralized with 4.09 ml (29.40 mmol) of triethylamine. The residue was dissolved in diethyl ether and cold water. The reaction was extracted with 10% aq. KHSO4 solution/EtOAc (3×). The organic phases were washed with 10% aq. KHSO4 solution, dried over Na2SO4 and evaporated. Flash silica gel column (CH2Cl2/MeOH 99:2 to 9:1) afforded 0.57 g (74%) of the title compound as a 61:39 mixture of the (R) and (S) diastereomers as brown oil. MS: 389.09 (M−H−, Cl).

Workup

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

Sources & evidence

ORD record
ord-175fe92a728a4f8ebb3eb50cc1d9bde4
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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