Diisopropylethylamine → Ethyl(2S)-3-[4-(2-{butyl[2-fluoro-4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoate

HRID 1725214Notes

Reaction equation

HRID 1725214 reaction equation
[CH2:1]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[F:17])[CH2:2][CH2:3][CH3:4].[CH2:18]([O:20][C@H:21]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:22][C:23]1[CH:33]=[CH:32][C:26]([O:27][CH2:28][C:29](O)=[O:30])=[CH:25][CH:24]=1)[CH3:19].C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:1]([N:5]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:14])([F:15])[F:16])=[CH:9][C:8]=1[F:17])[C:29](=[O:30])[CH2:28][O:27][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][C@H:21]([O:20][CH2:18][CH3:19])[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:33][CH:32]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11162260{4-[(2S)-2,3-Diethoxy-3-oxopropyl]phenoxy}acetic AcidHCID 68855369Benzenemethanamine, N-butyl-2-fluoro-4-(trifluoromethyl)-

Product 1

HCID 68855512Ethyl(2S)-3-[4-(2-{butyl[2-fluoro-4-(trifluoromethyl)benzyl]amino}-2-oxoethoxy)phenyl]-2-ethoxypropanoateYield 74.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N-butyl-N-[2-fluoro-4-(trifluoromethyl)benzyl]amine (0.598 g, 2.40 mmol) and {4-[(2S)-2,3-diethoxy-3-oxopropyl]phenoxy}acetic acid (0.593 g, 2.00 mmol) in methylene chloride (20 mL) were added N,N-diisopropylethylamine (0.80 mL, 4.6 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (0.674 g, 2.10 mmol) and the reaction mixture was stirred at room temperature overnight. The resulting solution was diluted with methylene chloride (100 mL) and the organic phase was washed with 2 M HCl (3×75 mL), saturated aqueous NaHCO3 (2×75 mL), and brine (75 mL), dried over Na2SO4, and concentrated in vacuo. Purification on a prepacked column of silica gel (Isolute® SPE Column, 20 g/70 mL) with methanol (0-2% gradient) in methylene chloride as the eluent yielded 0.785 g (74%) of a pale yellowish-white oil.

Workup

  1. washthe organic phase was washed with 2 M HCl (3×75 mL), saturated aqueous NaHCO3 (2×75 mL), and brine (75 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customPurification on a prepacked column of silica gel (Isolute® SPE Column, 20 g/70 mL) with methanol (0-2% gradient) in methylene chloride as the eluent

Sources & evidence

ORD record
ord-e0866fd340ff4055899ddf3804aa0743
Source dataset
uspto-grants-2009_02
Patent number
US07488844B2

Reaction notes

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