Benzyl Alcohol → HCID 131713407, compound

HRID 1388755Notes

Reaction equation

HRID 1388755 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:40]([N:42]1[CH2:56][CH2:55][CH2:54][C@H:43]1[C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])=[O:41])[CH3:39].N1CCC[C@H]1C(OCC1C=CC=CC=1)=O>C1C=CC=CC=1.O1CCCC1.C(OCC)(=O)C.CC(C)=O.C1(C)C=CC=CC=1.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:40]([N:42]2[CH2:56][CH2:55][CH2:54][C@H:43]2[C:44]([O:46][CH2:47][C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:45])=[O:41])[CH3:39])=[O:15])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

11

Reactant 5

HCID 244Benzyl AlcoholHCID 24819Phosphorus pentachlorideHCID 736155Benzyl L-prolinateHCID 13034412L-alanyl-L-proline, phenylmethyl ester, hydrochlorideHCID 23314622(6-Phthalimidohexyl)phosphonic acid

Product 1

HCID 131713407HCID 131713407, compound

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolventHCID 20247278Toluene acetoneSolvent

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 minutes and then treated with L-alanyl-L-proline, phenylmethyl ester, hydrochloride (2.40 g., 7.68 mmole). 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.) eluting with acetone-hexane (1:1) to give 1.75 g. of 1-[N-[phenylmethoxy)(6-phthalimidohexyl)phosphinyl]-L-alanyl]-L-proline, phenylmethyl ester as a colorless glass. Tlc (acetone-toluene; 1:1) shows a single spot at Rf =0.27.

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 minutes
  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.)
  16. washeluting with acetone-hexane (1:1)
  17. customto give 1.75 g

Sources & evidence

ORD record
ord-ce9eadbc1b8c4551bc1dc8b449b71cf3
Source dataset
uspto-grants-1984_02
Patent number
US04432971

Reaction notes

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