Benzyl Alcohol → HCID 131713400, compound

HRID 1388695Notes

Reaction equation

HRID 1388695 reaction equation
[C:1]1(=[O:21])[N:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][P:12](=[O:15])([OH:14])O)[C:4](=[O:16])[C:3]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:2]12.P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:28](O)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.Cl.[NH2:37][C@H:38]([C:46]([NH:48][C@H:49]([C:54]([O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:55])[CH2:50][CH:51]([CH3:53])[CH3:52])=[O:47])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1C=CC=CC=1.O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[C:29]1([CH2:28][O:14][P:12]([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][N:5]2[C:1](=[O:21])[C:2]3=[CH:20][CH:19]=[CH:18][CH:17]=[C:3]3[C:4]2=[O:16])([NH:37][C@H:38]([C:46]([NH:48][C@H:49]([C:54]([O:56][CH2:57][C:58]2[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=2)=[O:55])[CH2:50][CH:51]([CH3:53])[CH3:52])=[O:47])[CH2:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)=[O:15])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

9

Reactant 4

HCID 244Benzyl AlcoholHCID 24819Phosphorus pentachlorideHCID 23314622(6-Phthalimidohexyl)phosphonic acidHCID 70633701HCID 70633701, compound

Product 1

HCID 131713400HCID 131713400, compound

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of (6-phthalimidohexyl)phosphonic acid (2.34 g., 7.52 mmole) in dry benzene (10 ml.) is treated with phosphorus pentachloride (3.30 g., 15.9 mmole) and stirred at room temperature under argon for 45 minutes. The mixture is then refluxed for 15 minutes, cooled and evaporated to dryness (0.5 mm. Hg). The residue is taken up in dry tetrahydrofuran (10 ml.), cooled in an ice bath and treated dropwise with a solution of benzyl alcohol (0.81 g., 7.5 mmole) and triethylamine (1.05 ml., 7.59 mmole) in dry tetrahydrofuran (5 ml.) over a period of 20 minutes. The mixture is allowed to warm to room temperature, stirred for 30 minuted and then treated with a slight molar excess of L-phenylalanyl-L-leucine, phenylmethyl ester, hydrochloride salt. The resulting suspension is cooled in an ice-bath and treated dropwise with a solution of triethylamine (4.5 ml.) in tetrahydrofuran (8 ml.). The mixture is warmed to room temperature, stirred for 1.5 hours, diluted with ethyl acetate, filtered and evaporated. The residue is taken up in ethyl acetate and 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 (100 g.) to give N-[N-[(phenylmethoxy)(6-phthalimidohexyl)phosphinyl]-L-phenylalanyl]-L-leucine, phenylmethyl ester.

Workup

  1. temperatureThe mixture is then refluxed for 15 minutes
  2. temperaturecooled
  3. customevaporated to dryness (0.5 mm. Hg)
  4. temperaturecooled in an ice bath
  5. temperatureto warm to room temperature
  6. stirringstirred for 30 minuted
  7. temperatureThe resulting suspension is cooled in an ice-bath
  8. temperatureThe mixture is warmed to room temperature
  9. stirringstirred for 1.5 hours
  10. filtrationfiltered
  11. customevaporated
  12. washwashed successively with 5% potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride
  13. dry with materialdried (Na2SO4)
  14. customevaporated
  15. customThe residue is purified by flash chromatography on silica gel (100 g.)

Sources & evidence

ORD record
ord-46f9a76d1a454d7587640023130946d5
Source dataset
uspto-grants-1984_02
Patent number
US04432972

Reaction notes

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