Diethyl Ether → 1-[N-[ethoxy(4-phenylbutyl)phosphinyl]-L-alanyl]-L-proline, phenylmethyl ester

HRID 1388747Notes

Reaction equation

HRID 1388747 reaction equation
ClCl.[C:3]1([CH2:9][CH2:10][CH2:11][CH2:12][PH:13](=[O:15])[OH:14])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:16](OCC)[CH3:17].Cl.[NH2:22][C@H:23]([C:25]([N:27]1[CH2:41][CH2:40][CH2:39][C@H:28]1[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30])=[O:26])[CH3:24].C(N(CC)CC)C>C(Cl)(Cl)(Cl)Cl.C(OCC)(=O)C.O1CCCC1>[CH2:16]([O:15][P:13]([CH2:12][CH2:11][CH2:10][CH2:9][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)([NH:22][C@H:23]([C:25]([N:27]1[CH2:41][CH2:40][CH2:39][C@H:28]1[C:29]([O:31][CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)=[O:30])=[O:26])[CH3:24])=[O:14])[CH3:17]

Participants

9

Reactant 5

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 24526Chlorine2×HCID 13034412L-alanyl-L-proline, phenylmethyl ester, hydrochlorideHCID 178527055HCID 178527055, compound

Product 1

HCID 1317134021-[N-[ethoxy(4-phenylbutyl)phosphinyl]-L-alanyl]-L-proline, phenylmethyl ester

Reagents, catalysts & solvents 3

HCID 5943Carbon TetrachlorideSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A half saturated solution of dry chlorine in carbon tetrachloride is added dropwise by syringe to a solution of (4-phenylbutyl)phosphinic acid, ethyl ether (0.95 g., 4.2 mmole) in 4 ml. of dry carbon tetrachloride under argon until the yellow color of excess chlorine persists. The mixture is evaporated to dryness (0.1 mm Hg.), the colorless residue is taken up in 6 ml. of dry tetrahydrofuran and treated with L-alanyl-L-proline, phenylmethyl ester, hydrochloride salt (1.0 g., 3.2 mmole). The resulting suspension is cooled to 0° (ice bath) under argon and treated dropwise with a solution of triethylamine (1.1 ml., 7.95 mmole) in 5 ml. of dry tetrahydrofuran over a 15 minute period. After the addition is complete, the mixture is allowed to come to room temperature and stirred for an additional 30 minutes. The mixture is diluted with ethyl acetate, filtered and evaporated to dryness. The residue is taken up in ethyl acetate, washed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride, dried (Na2SO4) and evaporated. The residue is purified by flash chromatography on silica gel (95 g.) eluting first with acetone/hexane (2:3) then acetone/hexane (2:1) to give 1.35 g of 1-[N-[ethoxy(4-phenylbutyl)phosphinyl]-L-alanyl]-L-proline, phenylmethyl ester as a colorless viscous oil. Rf (dichloromethane/acetone, 2:1) is 0.24.

Workup

  1. customThe mixture is evaporated to dryness (0.1 mm Hg.)
  2. temperatureThe resulting suspension is cooled to 0° (ice bath) under argon
  3. additionAfter the addition
  4. customto come to room temperature
  5. filtrationfiltered
  6. customevaporated to dryness
  7. washwashed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customThe residue is purified by flash chromatography on silica gel (95 g.)
  11. washeluting first with acetone/hexane (2:3)

Sources & evidence

ORD record
ord-34c25e5b61b9438fb020707c36318a02
Source dataset
uspto-grants-1984_02
Patent number
US04432971

Reaction notes

Loading…