Triethylamine → (+/-)-Dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester

HRID 1462487Notes

Reaction equation

HRID 1462487 reaction equation
Cl[P:2]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:6])[O:3][CH2:4][CH3:5].[NH2:17][CH:18]1[C:24](=[O:25])[N:23]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:22]2[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=2[S:20][CH2:19]1.C(N(CC)CC)C>O1CCCC1>[CH2:4]([O:3][P:2]([NH:17][CH:18]1[C:24](=[O:25])[N:23]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:22]2[CH2:32][CH:33]=[CH:34][CH:35]=[C:21]2[S:20][CH2:19]1)([CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:6])[CH3:5]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15591238Ethoxy(4-phenylbutyl)phosphinyl chlorideHCID 15591257(+/-)-3-amino-3,4-dihydro-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester

Product 1

HCID 86739551(+/-)-Dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of crude chloro (4-phenylbutyl)phosphinic acid, ethyl ester (2.44 mmole), dry tetrahydrofuran (10 ml.), and (±)-3-amino-3,4-dihydro-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester (0.65 g., 2.05 mmole) at 0° (ice bath) in an argon atmosphere is treated dropwise with triethylamine (0.86 ml., 3.0 eq.) in tetrahydrofuran (5 ml.) over 1 minute. After standing at 0° for 20 minutes the ice bath is removed and the reaction mixture is stirred for 16 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 (1.2 g.) is chromatographed on silica (60 g.) eluting with acetone/hexane (1:1) to give 0.8 g. of (±)-dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester as an oil after evaporation. TLC (acetone/hexane; 2:1) two spots at Rf =0.59,0.65(isomers at phosphorus).

Workup

  1. customthe ice bath is removed
  2. additionThe reaction mixture is diluted with ethyl acetate
  3. washwashed successively with saturated sodium bicarbonate, 5% potassium bisulfate and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue (1.2 g.) is chromatographed on silica (60 g.)
  7. washeluting with acetone/hexane (1:1)
  8. customto give 0.8 g
  9. customof (±)-dihydro-3-[[ethoxy(4-phenylbutyl)phosphinyl]amino]-4-oxo-1,5-benzothiazepine-5(2H)-acetic acid, ethyl ester as an oil after evaporation

Sources & evidence

ORD record
ord-b4c189789df445ecaa960be48136e495
Source dataset
uspto-grants-1984_07
Patent number
US04460579

Reaction notes

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