Diisopropylethylamine → N-[[1-[4-(methylthio)butyl]cyclopentyl]carbonyl]-4-nitro-L-phenylalanine methyl ester

HRID 990138Notes

Reaction equation

HRID 990138 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:17])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)[NH2:6].[CH3:18][S:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]1([C:29](O)=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:17])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)[NH:6][C:29]([C:24]1([CH2:23][CH2:22][CH2:21][CH2:20][S:19][CH3:18])[CH2:28][CH2:27][CH2:26][CH2:25]1)=[O:30]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11715866Methyl 4-nitro-L-phenylalaninate hydrochlorideHCID 226601431-[4-(Methylthio)butyl]cyclopentanecarboxylic acid

Product 1

HCID 57296143N-[[1-[4-(methylthio)butyl]cyclopentyl]carbonyl]-4-nitro-L-phenylalanine methyl esterYield 78.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-nitro-L-phenylalanine methyl ester hydrochloride salt (181.84 mmol, 47.41 g), 1-[4-(methylthio)butyl]cyclopentanecarboxylic acid (177.17 mmol, 38.33 g) in DMF (470 mL) were added HBTU (177.17 mmol, 67.2 g) and diisopropylethylamine (443 mmol, 77 mL) at room temperature. The clear solution was stirred for 15 h at room temperature at which time TLC analysis of the mixture indicated the absence of starting materials. The reaction mixture was diluted with 600 mL of ethyl acetate then was washed in turn with 0.5N hydrochloric acid (2×250 mL), saturated sodium bicarbonate solution (2×250 mL) and brine (300 mL). The dried (MgSO4) organic layer was filtered and evaporated to dryness under reduced pressure. The crude product which was purified by silica gel column chromatography to afford 58.5 g (78%) of N-[[1-[4-(methylthio)butyl]cyclopentyl]carbonyl]-4-nitro-L-phenylalanine methyl ester as an amorphous colorless solid. HRMS: Obs. mass, 423.1940. Calcd. mass, 423.1953 (M+H).

Workup

  1. washthen was washed in turn with 0.5N hydrochloric acid (2×250 mL), saturated sodium bicarbonate solution (2×250 mL) and brine (300 mL)
  2. dry with materialThe dried (MgSO4) organic layer
  3. filtrationwas filtered
  4. customevaporated to dryness under reduced pressure
  5. customThe crude product which was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-736f9a259a1041ffa567aef9da07d37f
Source dataset
uspto-grants-2002_10
Patent number
US06458844B2

Reaction notes

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