Triethylamine → HCID 13945819, compound

HRID 1252838Notes

Reaction equation

HRID 1252838 reaction equation
[C:1]1([CH2:7][CH2:8][P:9](=O)([O:18]CC2C=CC=CC=2)[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[C:33]1([CH2:39][O:40][C:41]([NH:43][CH2:44][CH2:45][CH2:46][CH2:47][C@H:48]([OH:66])[C:49]([N:51]2[CH2:65][CH2:64][CH2:63][C@H:52]2[C:53]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[O:54])=[O:50])=[O:42])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C>C1C=CC=CC=1>[C:1]1([CH2:7][CH2:8][P:9]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([O:66][C@@H:48]([CH2:47][CH2:46][CH2:45][CH2:44][NH:43][C:41]([O:40][CH2:39][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:42])[C:49]([N:51]2[CH2:65][CH2:64][CH2:63][C@H:52]2[C:53]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[O:54])=[O:50])=[O:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 24819Phosphorus pentachlorideHCID 13630870Dibenzyl (2-phenylethyl)phosphonateHCID 13934652HCID 13934652, compound

Product 1

HCID 13945819HCID 13945819, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of (2-phenylethyl)phosphonic acid, dibenzyl ester (1.48 g., 4.04 mmole, 1.5 eq.) in dry benzene (15 ml.) is treated with phosphorus pentachloride (952 mg., 4.57 mmole, 1.7 eq.) and the solution is heated at 75° (oil bath) for 2.5 hours under argon. The mixture is evaporated to dryness (0.5 mm of Hg.), taken up in benzene (10 ml.), and evaporated. This procedure is repeated twice. The clear residue is taken up in dry methylene chloride (15 ml.), 1-[(S)-6-[[(phenylmethoxy)carbonyl]amino]-2-hydroxy-1-oxohexyl]-L-proline, phenylmethyl ester (1.26 g., 2.69 mmole, 1.0 eq.) is added, the mixture is cooled to 0° (ice-bath), then treated with triethylamine (0.56 ml., 4.04 mmole, 1.5 eq.) and dimethylaminopyridine (49 mg., 0.40 mmole, 0.15 eq.), stirred at 0° for 15 minutes, and then at room temperature for one hour. The mixture is partitioned between 5% potassium bisulfate and methylene chloride. The organic layer is washed with brine, dried over anhydrous sodium sulfate, and evaporated to a yellow oil. The crude oil is purified by flash chromatography (LPS-1 silica gel) eluting with hexane:acetone (7:3). Product containing fractions are pooled and evaporated to give 916 mg. of 1-[(S)-2-[[(2-phenylethyl)(phenylmethoxy)phosphinyl]oxy]-6-[[((phenylmethoxy)carbonyl]amino]-1-oxohexyl]-L-proline, phenylmethyl ester as a clear, colorless oil.

Workup

  1. temperaturethe solution is heated at 75° (oil bath) for 2.5 hours under argon
  2. customThe mixture is evaporated to dryness (0.5 mm of Hg.)
  3. customevaporated
  4. temperaturethe mixture is cooled to 0° (ice-bath)
  5. waitat room temperature for one hour
  6. customThe mixture is partitioned between 5% potassium bisulfate and methylene chloride
  7. washThe organic layer is washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customevaporated to a yellow oil
  10. customThe crude oil is purified by flash chromatography (LPS-1 silica gel)
  11. washeluting with hexane:acetone (7:3)
  12. additionProduct containing fractions
  13. customevaporated
  14. customto give 916 mg

Sources & evidence

ORD record
ord-fc2f70e249154c2a880cf51beb78135d
Source dataset
uspto-grants-1988_05
Patent number
US04745196

Reaction notes

Loading…