Chlorine → 1-[N2-[(4-Phenylbutyl)(phenylmethoxy)phosphinyl]-N6-[(phenylmethoxy)carbonyl]-L-lysyl]-L-proline, phenylmethyl ester

HRID 1388749Notes

Reaction equation

HRID 1388749 reaction equation
ClCl.[C:3]1([CH2:9][CH2:10][CH2:11][CH2:12][PH:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl.[C:24]1([CH2:30][O:31][C:32]([NH:34][CH2:35][CH2:36][CH2:37][CH2:38][C@@H:39]([C:41]([N:43]2[CH2:57][CH2:56][CH2:55][C@H:44]2[C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:46])=[O:42])[NH2:40])=[O:33])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)(Cl)(Cl)Cl.C(OCC)(=O)C.ClCCl.CC(C)=O.O1CCCC1.C(N(CC)CC)C>[C:3]1([CH2:9][CH2:10][CH2:11][CH2:12][P:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([NH:40][C@H:39]([C:41]([N:43]2[CH2:57][CH2:56][CH2:55][C@H:44]2[C:45]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:46])=[O:42])[CH2:38][CH2:37][CH2:36][CH2:35][NH:34][C:32]([O:31][CH2:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:33])=[O:22])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 3

HCID 24526Chlorine2×HCID 1317134041-[N6-[(phenylmethoxy)carbonyl]-L-lysyl]-L-proline, phenylmethyl ester, hydrochloride saltHCID 178527035HCID 178527035, compound

Product 1

HCID 541590451-[N2-[(4-Phenylbutyl)(phenylmethoxy)phosphinyl]-N6-[(phenylmethoxy)carbonyl]-L-lysyl]-L-proline, phenylmethyl ester

Reagents, catalysts & solvents 5

HCID 5943Carbon TetrachlorideSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 21584124Propan-2-one--dichloromethane (1/1)Solvent

Procedure

A half saturated solution of dry chlorine in carbon tetrachloride is added dropwise by syringe to a solution of (4-phenylbutyl)phosphinic acid, phenylmethyl ester (1.0 g., 3.47 mmole), from Example 1 (c), in 5 ml. of dry carbon tetrachloride under argon until the yellow color of excess chlorine persists. The mixture is evaporated to dryness (0.15 mm. of Hg), and the residue is taken up in 5 ml. of dry tetrahydrofuran and treated with 1-[N6 -[(phenylmethoxy)carbonyl]-L-lysyl]-L-proline, phenylmethyl ester, hydrochloride salt (1.74 g., 3.4 mmole). The resulting suspension is cooled to 0° (ice bath) under argon and treated dropwise with a solution of triethylamine (1.2 ml.) in 6 ml. of dry tetrahydrofuran over a 15 minute period. After the addition is complete, the mixture is stirred at 0° for 15 minutes, then allowed to warm to room temperature and stirred for an additional one hour. 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, water, saturated sodium bicarbonate, saturated sodium chloride, dried (Na2SO4), and evaporated. The residue (3.2 g.) is purified by flash chromatography on silica gel (120 g.) eluting with dichloromethane-hexane (5:1) to give 1.62 g. of 1-[N2 -[(4-phenylbutyl)(phenylmethoxy)phosphinyl]-N6 -[(phenylmethoxy)carbonyl]-L-lysyl]-L-proline,phenyl methyl ester as a colorless oil. Tlc (dichloromethane/acetone; 4:1) single spot at Rf 0.42.

Workup

  1. customThe mixture is evaporated to dryness (0.15 mm. of Hg)
  2. temperatureThe resulting suspension is cooled to 0° (ice bath) under argon
  3. additionAfter the addition
  4. stirringstirred for an additional one hour
  5. filtrationfiltered
  6. customevaporated to dryness
  7. washwashed successively with 5% potassium bisulfate, water, saturated sodium bicarbonate, saturated sodium chloride
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customThe residue (3.2 g.) is purified by flash chromatography on silica gel (120 g.)
  11. washeluting with dichloromethane-hexane (5:1)
  12. customto give 1.62 g

Sources & evidence

ORD record
ord-fc79ed42bcec4882aa89b0e067be11cd
Source dataset
uspto-grants-1984_02
Patent number
US04432971

Reaction notes

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