Benzyl Alcohol → HCID 131713397, compound

HRID 1388693Notes

Reaction equation

HRID 1388693 reaction equation
[C:1]1([P:7](Cl)(Cl)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:11]([OH:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.Cl.[NH2:27][C@H:28]([C:36]([NH:38][C@H:39]([C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>ClCCl>[C:12]1([CH2:11][O:18][P:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([NH:27][C@H:28]([C:36]([NH:38][C@H:39]([C:44]([O:46][CH2:47][C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:45])[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:37])[CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:8])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471Triethylamine2×HCID 69990Phenylphosphonic dichlorideHCID 70633701HCID 70633701, compound

Product 1

HCID 131713397HCID 131713397, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of phenylphosphonic dichloride (1.15 ml., 8 mmole) and dry dichloromethane (15 ml.) under argon at 25° is treated dropwise with benzyl alcohol (0.83 ml., 1 eq.) and triethylamine (1.1 ml., 1 eq.) in dichloromethane (5 ml.) over a 20 minute period. A slight exotherm is observed. The reaction mixture is then refluxed for 15 minutes, cooled to 0° (ice bath), and L-phenylalanyl-L-leucine, phenylmethyl ester, hydrochloride salt (1 eq.) is added. The heterogeneous mixture is treated dropwise with triethylamine (2.4 ml., 2.1 eq.) in dichloromethane (8 ml.) over a 5 minute period. The ice bath is removed and the reaction mixture is stirred for an additional 1.5 hours. The solids are removed by filtration and the dichloromethane is stripped from the filtrate. The residue is taken up in ethyl acetate and washed with water, saturated sodium bicarbonate, 5% potassium bisulfate, saturated sodium bicarbonate, brine, dried (MgSO4), and evaporated to a residue. The residue is purified chromatographically to give N-[N-[phenylmethoxy(phenyl)phosphinyl]-L-phenylalanyl]-L-leucine, phenylmethyl ester.

Workup

  1. temperatureThe reaction mixture is then refluxed for 15 minutes
  2. additionis added
  3. customThe ice bath is removed
  4. customThe solids are removed by filtration
  5. washwashed with water, saturated sodium bicarbonate, 5% potassium bisulfate, saturated sodium bicarbonate, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to a residue
  8. customThe residue is purified chromatographically

Sources & evidence

ORD record
ord-376a4de861cc462aa607956cda695741
Source dataset
uspto-grants-1984_02
Patent number
US04432972

Reaction notes

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