Diphenylphosphinic chloride → HCID 70510866, compound

HRID 1262883Notes

Reaction equation

HRID 1262883 reaction equation
C(N(C(C)C)CC)(C)C.C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.[C:25]([O:29][C:30]([N:32]([CH3:49])[C@H:33]([C:46](O)=[O:47])[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:37][CH:36]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].Cl.[C:51]1([CH2:57][CH2:58][CH2:59][NH:60][C:61](=[O:68])[C@@H:62]([CH2:64][CH2:65][S:66][CH3:67])[NH2:63])[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>O1CCCC1>[C:25]([O:29][C:30]([N:32]([CH3:49])[C@H:33]([C:46]([NH:63][C@@H:62]([C:61]([NH:60][CH2:59][CH2:58][CH2:57][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)=[O:68])[CH2:64][CH2:65][S:66][CH3:67])=[O:47])[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][C:42]([CH3:44])([CH3:45])[CH3:43])=[CH:37][CH:36]=1)=[O:31])([CH3:26])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×HCID 54000823N-[(1,1-Dimethylethoxy)carbonyl]-O-(1,1-dimethylethyl)-N-methyl-L-tyrosineHCID 70510997HCID 70510997, compound

Product 1

HCID 70510866HCID 70510866, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

Diisopropylethylamine (0.90 ml.), then diphenylphosphinyl chloride (1.23 g.), were added to a solution of N-(tert-butyloxycarbonyl)-O-(tert-butyl)-N-methyl-L-tyrosine (1.76 g.) in tetrahydrofuran (15 ml.) maintained at -20° C., and the mixture was stirred for ten minutes. A solution of N-(3-phenylpropyl)-D-methioninamide hydrochloride (1.58 g.) and diisopropylethylamine (0.90 ml.) in tetrahydrofuran (10 ml.) was then added. The mixture was stirred for one half hour at -20°, one hour at 0° C. and overnight at room temperature, then filtered and stripped of solvent. A solution of the residue in ethyl acetate (100 ml.) was washed with water, aqueous citric acid, water again, aqueous sodium bicarbonate and water again, dried and stripped of solvent. Purification of the residue by high pressure liquid chromatography on silica gel (350 g.) using hexane-ethyl acetate (2:1) as the eluant afforded in fractions 6-7 (k'=8-14) [N-(tert-butyloxycarbonyl)-O-(tert-butyl)-N-methyl-L-tyrosyl]-N-(3-phenylpropyl)-D-methioninamide as a clear gum (2.1 g.).

Workup

  1. stirringThe mixture was stirred for one half hour at -20°, one hour at 0° C. and overnight at room temperature
  2. filtrationfiltered
  3. washA solution of the residue in ethyl acetate (100 ml.) was washed with water, aqueous citric acid, water again
  4. dry with materialaqueous sodium bicarbonate and water again, dried
  5. customPurification of the residue by high pressure liquid chromatography on silica gel (350 g.)

Sources & evidence

ORD record
ord-214dff10a3984679bf10cc884e0c0e85
Source dataset
uspto-grants-1984_06
Patent number
US04454120

Reaction notes

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