Triethylamine → {[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-tert-butyl-amino}-acetic acid ethyl ester

HRID 1665256Notes

Reaction equation

HRID 1665256 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=3)[C:20](Cl)=[O:21])=[CH:11][CH:10]=2)=[C:4]([O:26][CH3:27])[CH:3]=1.C([N:30](CC)CC)C.COC(=O)[C@H:38]([C:40]([CH3:43])(C)[CH3:41])N.[CH3:45][CH2:46][O:47][C:48]([CH3:50])=[O:49]>C1COCC1>[CH2:46]([O:47][C:48](=[O:49])[CH2:50][N:30]([C:20](=[O:21])[C:19]1[CH:23]=[CH:24][CH:25]=[C:17]([CH2:16][O:15][C:12]2[CH:13]=[CH:14][C:9]([C:5]3[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=3[O:26][CH3:27])=[CH:10][CH:11]=2)[CH:18]=1)[C:40]([CH3:43])([CH3:41])[CH3:38])[CH3:45]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 11309583Methyl L-tert-leucinateHCID 866535923-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoyl chloride

Product 1

HCID 67152350{[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-tert-butyl-amino}-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoyl chloride (10 g, 25.7 mmol), triethylamine (10 mL, 64 mmol) in anhydrous THF (50 mL) was added in portions of tert-butylglycine methyl ester at 0° C., followed by slowly warming up to room temperature overnight while stirring. The mixture was diluted with EtOAc, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The oily residue was purified by column (0-30% EtOAc in hexane) to give {[3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-benzoyl]-tert-butyl-amino}-acetic acid ethyl ester, 11.6 g (91%). LC-MS (ES) calculated for C28H29F2NO5, 497; found m/z 498 [M+H]+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe oily residue was purified by column (0-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-7d423d06898c464dad4b82b31cfd7815
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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