1,1'-Carbonyldiimidazole → HCID 53883900, compound

HRID 1489795Notes

Reaction equation

HRID 1489795 reaction equation
[OH:1][P:2]([CH2:5][CH:6]([CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:7]([OH:9])=O)([CH3:4])=[O:3].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:30]1([NH:36][C:37](=[O:44])[C@H:38]([CH2:40][CH:41]([CH3:43])[CH3:42])[NH2:39])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>O1CCCC1.C(OCC)(=O)C>[C:30]1([NH:36][C:37](=[O:44])[C@H:38]([CH2:40][CH:41]([CH3:42])[CH3:43])[NH:39][C:7](=[O:9])[CH:6]([CH2:5][P:2]([OH:1])([CH3:4])=[O:3])[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 11031002L-leucine anilideHCID 22902421HCID 22902421, compound

Product 1

HCID 53883900HCID 53883900, compoundYield 94.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A portion (313 mg) of the crude 2-((hydroxy(methyl)phosphinyl)methyl)-4-phenylbutanoic acid from Step B was dissolved in tetrahydrofuran (3.0 mL) and 4 Å molecular sieves (0.40 g) were added. The mixture was stirred at room temperature and 1,1'-carbonyldiimidazole (215 mg, 1.33 mmol) was added, followed 15 min later by L-leucine N-phenylamide (297 mg, 1.44 mmol).7After 22 h, the mixture was diluted with ethyl acetate (30 mL) and washed with 2N aqueous hydrochloric acid (2×15 mL) and saturated aqueous sodium chloride (15 mL). The organic layer was dried (sodium sulfate) decanted, and evaporated to give 511 mg of colorless foam. The two diastereomers of a portion (145 mg) of the crude product were separated by high pressure liquid chromatography on a 22 mm×25 cm reverse phase column (Whatman ODS-3, Partisil 10) eluting with 60% methanol/40% water/0.05% trifluoroacetic acid (flow rate of 25 mL/min, detection at 250 nm). This yielded the more mobile isomer (43 mg, 31% yield for Steps B-C) and the less mobile isomer (51 mg, 36% yield for Steps B-C), both obtained as brittle films.

Workup

  1. addition4 Å molecular sieves (0.40 g) were added
  2. washwashed with 2N aqueous hydrochloric acid (2×15 mL) and saturated aqueous sodium chloride (15 mL)
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customdecanted
  5. customevaporated

Sources & evidence

ORD record
ord-0bc7b06edc674ebfa3308f37c7e0d5b9
Source dataset
uspto-grants-1997_10
Patent number
US05679700

Reaction notes

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