Trifluoroacetic acid → [2-(1-Azido-2-{3-[2-(2,2,2-trifluoroacetylamino)-ethylcarbamoyl]phenoxy}ethoxy)ethoxy]acetic acid ethyl ester

HRID 661194Notes

Reaction equation

HRID 661194 reaction equation
[N:1]([CH:4]([O:16][CH2:17][CH2:18][O:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:5][O:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1C(O)=O)=[N+:2]=[N-:3].C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)C(=O)C1.[F:44][C:45]([F:50])([F:49])[C:46](O)=[O:47].[NH2:51][CH2:52][CH2:53][NH:54][C:55](=[O:60])C(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH2:24]([O:23][C:21](=[O:22])[CH2:20][O:19][CH2:18][CH2:17][O:16][CH:4]([N:1]=[N+:2]=[N-:3])[CH2:5][O:6][C:7]1[CH:8]=[CH:12][CH:13]=[C:14]([C:55](=[O:60])[NH:54][CH2:53][CH2:52][NH:51][C:46](=[O:47])[C:45]([F:50])([F:49])[F:44])[CH:15]=1)[CH3:25]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 229755N-(2-aminoethyl)-2,2,2-trifluoroacetamideHCID 676246Di(succinimido) carbonateHCID 86628347(2-Azido-2-(2-ethoxycarbonylmethoxy-ethoxy)-ethoxy]-benzoic acid

Product 1

HCID 59771759[2-(1-Azido-2-{3-[2-(2,2,2-trifluoroacetylamino)-ethylcarbamoyl]phenoxy}ethoxy)ethoxy]acetic acid ethyl esterYield 86.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

3-[(2-Azido-2-(2-ethoxycarbonylmethoxy-ethoxy)-ethoxy]-benzoic acid (0.212 g, 0.6 mmol) was stirred with N,N′-disuccinimidyl carbonate (0.184 g, 0.72 mmol) and DMAP (0.088 g, 0.72 mmol) in dry DMF (1 ml) at room temperature. After 10 minutes, trifluoroacetic acid salt of N-(2-amino-ethyl)-2,2,2-trifluoro-acetamide (0.194 g, 0.72 mmol) was added followed by diisopropylethylamine (DIPEA) (0.251 ml, 1.44 mmol). The reaction mixture was then stirred at room temperature for 17 hours. All the solvents were evaporated under reduced pressure and the residues were partitioned between DCM (50 ml) and aqueous NaH2PO4 (1 N, 50 ml). The aqueous layer was further extracted with DCM (2×25 ml). All the DCM extracts were combined, dried over MgSO4 and evaporated under reduced pressure. The residue was purified by column chromatography (1×20 cm). The title compound, eluted with 1% methanol in DCM, was obtained as an oil (0.255 g, 86.6%). ES-MS, m/z 490.10 (M−1).

Workup

  1. customAll the solvents were evaporated under reduced pressure
  2. customthe residues were partitioned between DCM (50 ml) and aqueous NaH2PO4 (1 N, 50 ml)
  3. extractionThe aqueous layer was further extracted with DCM (2×25 ml)
  4. dry with materialdried over MgSO4
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography (1×20 cm)
  7. washThe title compound, eluted with 1% methanol in DCM

Sources & evidence

ORD record
ord-d8813e71152a4743a85b9a92064c09b4
Source dataset
uspto-grants-2011_12
Patent number
US08084590B2

Reaction notes

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