Triethylamine → HCID 67153754, compound

HRID 547851Notes

Reaction equation

HRID 547851 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-])=O)[CH:18]=2)=[CH:11][CH:10]=1.[CH2:26]([O:33][C:34]([C@@H:36]1[CH2:40][CH2:39][CH2:38][C@H:37]1[C:41](O)=[O:42])=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CCO.Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O.[Pd]>[CH2:26]([O:33][C:34]([C@@H:36]1[CH2:40][CH2:39][CH2:38][C@H:37]1[C:41](=[O:42])[NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([CH2:16][O:15][C:12]2[CH:13]=[CH:14][C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:10][CH:11]=2)[CH:18]=1)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

11

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 582877952,4-Difluoro-4'-(3-nitro-benzyloxy)-biphenylHCID 66738496HCID 66738496, compound

Product 1

HCID 67153754HCID 67153754, compoundYield 43.9%

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2,4-difluoro-4′-(3-nitro-benzyloxy)-biphenyl (26.3 mg, 0.077 mmol) and 10% Pd/C (5.3 mg) in EtOH (3 mL) containing 2 drops 2N HCl was hydrogenated at 50 psi for 2 hrs. The reaction mixture was filtered and evaporated. The crude product was dissolved in DMF (1 mL) with rac-(trans)-cyclopentane-1,2-dicarboxylic acid monobenzyl ester (19.5 mg, 0.77 mmol), triethylamine (32 uL, 0.231 mmol) and BOP (33 mg, 0.077 mmol). The mixture was stirred for 1 hr at RT. DMAP (1 mg) was added and stirring continued overnight. The reaction mixture was diluted with EtOAc (20 mL), washed with 2.5% KHSO4 (3×10 mL), 50% saturated NaHCO3 (10 mL), saturated NaCl (10 mL), dried over MgSO4, filtered and evaporated. The crude ester was purified by flash chromatography with a 0-20% gradient of ethyl acetate in hexanes to yield 18.3 mg of (trans)-2-[3-(2′,4′-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid benzyl ester as a clear oil. This material was dissolved in EtOH (3 mL) with 10% Pd/C (4 mg) and hydrogenated at 50 psi for 1 hr. The reaction mixture was filtered through Celite and evaporated to give (trans)-2-[3-(2′,4′-difluoro-biphenyl-4-yloxymethyl)-phenylcarbamoyl]-cyclopentanecarboxylic acid as a white solid (16.4 mg, 47%). LC-MS (ES) calculated for C26H23F2NO4, 451.47; found m/z 450.2 [M−H]−.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated
  3. stirringstirring continued overnight
  4. washwashed with 2.5% KHSO4 (3×10 mL), 50% saturated NaHCO3 (10 mL), saturated NaCl (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude ester was purified by flash chromatography with a 0-20% gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6b0dc9bb3a3b447c9116d72e345d019a
Source dataset
uspto-grants-2011_05
Patent number
US07939569B1

Reaction notes

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