Triethylamine → (S)-Hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester

HRID 745342Notes

Reaction equation

HRID 745342 reaction equation
[CH2:1]([O:3][P:4](Cl)([CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:5])[CH3:2].Cl.[NH2:18][CH:19]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:20]1=[O:32].C(N(CC)CC)C>O1CCCC1>[CH2:1]([O:3][P:4]([NH:18][C@H:19]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:20]1=[O:32])([CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15591238Ethoxy(4-phenylbutyl)phosphinyl chlorideHCID 1317142923-amino-2-oxo-hexahydro-1H-azepine-1-acetic acid, ethyl ester, monohydrochloride

Product 1

HCID 86740216(S)-Hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of ethoxy(4-phenylbutyl)phosphinyl chloride [4.4 mmole; prepared as set forth in Example 1(f)], dry tetrahydrofuran (10 ml.), and 3-amino-2-oxo-hexahydro-1H-azepine-1-acetic acid, ethyl ester, monohydrochloride (1.0 g., 4.0 mmole) at 0° (ice bath) in an argon atmosphere is treated dropwise with triethylamine (1.7 ml., 3.0 eq.) in tetrahydrofuran (5 ml.) over 2 minutes. After 20 minutes, the ice bath is removed and the reaction mixture is stirred for an additional 1.5 hours. The reaction mixture is diluted with ethyl acetate and washed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and brine, dried (MgSO4) and evaporated. The residue (2.1 g.) is chromatographed on silica (65 g.) eluting with ethyl acetate then acetone to give 1.0 g. of (S)-hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester as an oil after evaporation. TLC (ethyl acetate) single spot at Rf =0.1.

Workup

  1. customprepared
  2. customat 0°
  3. customthe ice bath is removed
  4. additionThe reaction mixture is diluted with ethyl acetate
  5. washwashed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and brine
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe residue (2.1 g.) is chromatographed on silica (65 g.)
  9. washeluting with ethyl acetate
  10. customacetone to give 1.0 g
  11. customof (S)-hexahydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-2-oxo-1H-azepine-1-acetic acid, ethyl ester as an oil after evaporation

Sources & evidence

ORD record
ord-e3fd677cfe884510bbd2b8d94105c887
Source dataset
uspto-grants-1986_07
Patent number
US04598071

Reaction notes

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