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

HRID 1481957Notes

Reaction equation

HRID 1481957 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:8]=[C:9]([CH:13]=[CH:14][CH:15]=1)[C:10]([OH:12])=O)=[N+:2]=[N-:3].C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)C(=O)C1.FC(F)(F)C(O)=O.[NH2:51][CH2:52][CH2:53][NH:54][C:55](=[O:60])[C:56]([F:59])([F:58])[F:57].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:15]=[CH:14][CH:13]=[C:9]([C:10](=[O:12])[NH:51][CH2:52][CH2:53][NH:54][C:55](=[O:60])[C:56]([F:59])([F:58])[F:57])[CH:8]=1)[CH3:25]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 229755N-(2-aminoethyl)-2,2,2-trifluoroacetamideHCID 676246Di(succinimido) carbonateHCID 597717713-[2-Azido-2-(2-ethoxycarbonylmethoxyethoxy)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-11cd4e0f0d7e4f0e815356b055b6cbed
Source dataset
uspto-grants-2016_08
Patent number
US09410199B2

Reaction notes

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