Triethylamine → HCID 71599882, compound

HRID 1507703Notes

Reaction equation

HRID 1507703 reaction equation
[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=O)[NH2:23])[N:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]=1[C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C(OCC2C=CC=CC=2)=C(C(=O)N(C)C)N(C2C=CC(F)=CC=2)C=1C([O-])=O)C1C=CC=CC=1.C([NH+](CC)CC)C.[Cl-].[NH4+].C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22]#[N:23])[N:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]=1[C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 25517Ammonium ChlorideHCID 89610446HCID 89610446, compoundHCID 89610643HCID 89610643, compound

Product 1

HCID 71599882HCID 71599882, compoundYield 95.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 3,4-bis(benzyloxy)-5-carbamoyl-1-(4-fluorophenyl)-1H-pyrrole-2-carboxylate (15) (1.1 g, 2.25 mmol) [prepared using the same procedure as Example B step (v) using triethylammonium 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-fluorophenyl)-1H-pyrrole-2-carboxylate and ammonium chloride] and triethylamine (1.26 mL, 9.0 mmol) in DCM (60 mL) at 0° C. was added trifluoroacetic anhydride (0.48 mL 3.38 mmol). The reaction mixture was allowed to warm to RT and partitioned between 1M HCl (aq.) (25 mL) and DCM (50 mL) the organic layer was washed with 1M HCl (aq.), and sat. NaHCO3 (aq.) (25 mL), dried (MgSO4), filtered and the volatiles removed in vacuo to afford the crude product. The crude residue was purified by silica gel chromatography (40 g, 0-20% EtOAc in isohexane) to afford ethyl 3,4-bis(benzyloxy)-5-cyano-1-(4-fluorophenyl)-1H-pyrrole-2-carboxylate (UL1-060) (1.01 g, 94%) as yellow solid: m/z 471 (M+H)+ (ES+). 1H NMR (400 MHz, DMSO-d6) δ: 7.57-7.27 (m, 14H), 5.27 (s, 2H), 5.11 (s, 2H), 4.05 (q, J=7.1 Hz, 2H), 1.00 (t, J=7.1 Hz, 3H).

Workup

  1. customat 0° C.
  2. custompartitioned between 1M HCl (aq.) (25 mL) and DCM (50 mL) the organic layer
  3. washwas washed with 1M HCl (aq.), and sat. NaHCO3 (aq.) (25 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe volatiles removed in vacuo
  7. customto afford the crude product
  8. customThe crude residue was purified by silica gel chromatography (40 g, 0-20% EtOAc in isohexane)

Sources & evidence

ORD record
ord-c33cf235a57249d4a74fe19d53f58a11
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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