Dicyclohexylcarbodiimide → HCID 178523300, compound

HRID 1252840Notes

Reaction equation

HRID 1252840 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][PH:12](=[O:14])[OH:13])=[CH:4][CH:3]=1.[C:15]1([CH2:21][O:22][C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30](O)[C:31]([N:33]2[CH2:47][CH2:46][CH2:45][C@H:34]2[C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])=[O:32])=[O:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(N=C=NC2CCCCC2)CCCCC1.CN(C1C=CC=CN=1)C>O1CCCC1.C(OCC)(=O)C>[C:15]1([CH2:21][O:22][C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30]([O:14][PH:12]([CH2:11][CH2:10][CH2:9][CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[O:13])[C:31]([N:33]2[CH2:47][CH2:46][CH2:45][C@H:34]2[C:35]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)=[O:36])=[O:32])=[O:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 13934652HCID 13934652, compoundHCID 178527056HCID 178527056, compound

Product 1

HCID 178523300HCID 178523300, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

[4-(4-Fluorophenyl)butyl]phosphinic acid, 1-adamantanamine salt (1.18 g.) is partitioned between 1.0N hydrochloric acid and ethyl acetate. The organic phase is washed with brine and dried over anhydrous sodium sulfate. The mixture is evaporated to give 696 mg. of [4-(4-fluorophenyl)butyl]phosphinic acid. This acid (696 mg., 3.22 mmole, 1.5 eq.) is dissolved in dry tetrahydrofuran (15 ml.), combined with 1-[(S)-6-[[(phenylmethoxy)carbonyl]amino]-2-hydroxy-1-oxohexyl]-L-proline, phenylmethyl ester (1.01 g., 2.15 mmole, 1 eq.) and treated with dicyclohexylcarbodiimide (664 mg., 3.22 mmole, 1.5 eq.) and dimethylaminopyridine (39 mg., 0.15 eq.). The white suspension is stirred under argon for 1 hour at room temperature, then diluted with ethyl acetate, and filtered to remove dicyclohexyl urea. The filtrate is washed with 5% potassium bisulfate, saturated sodium bicarbonate, and brine, then dried over anhydrous sodium sulfate, and evaporated to an oily residue. Chromatography on a 3/4 inch pad of SiliCAR CC-7 silica gel eluting with ethyl ether:acetone (8:2) removes impurities. Product containing fractions are pooled and evaporated to give crude 1-[(S)-6-[[(phenylmethoxy)carbonyl]amino]-2-[[[4-(4-fluorophenyl)butyl]phosphinyl]oxy]-1-oxohexyl]-L-proline, phenylmethyl ester as an oil. TLC (silica gel; ethyl ether:acetone, 8:2) Rf =0.09.

Workup

  1. custom[4-(4-Fluorophenyl)butyl]phosphinic acid, 1-adamantanamine salt (1.18 g.) is partitioned between 1.0N hydrochloric acid and ethyl acetate
  2. washThe organic phase is washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe mixture is evaporated
  5. customto give 696 mg
  6. filtrationfiltered
  7. customto remove dicyclohexyl urea
  8. washThe filtrate is washed with 5% potassium bisulfate, saturated sodium bicarbonate, and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated to an oily residue
  11. customChromatography on a 3/4 inch pad of SiliCAR CC-7 silica gel eluting with ethyl ether:acetone (8:2) removes impurities
  12. additionProduct containing fractions
  13. customevaporated

Sources & evidence

ORD record
ord-79ca896405ec48bead5c83c36989b13e
Source dataset
uspto-grants-1988_05
Patent number
US04745196

Reaction notes

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