4-Methylmorpholine → methyl N-(tert-butoxycarbonyl)-L-leucyl-(5R)-5-((trimethylsilyl)ethynyl)-L-prolinate

HRID 1293339Notes

Reaction equation

HRID 1293339 reaction equation
[CH3:1][Si:2]([C:5]#[C:6][C@@H:7]1[NH:11][C@H:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8]1)([CH3:4])[CH3:3].CN(C1C=CC=CN=1)C.CN1CCOCC1.O.[C:33]([O:37][C:38]([NH:40][C@H:41]([C:46](O)=[O:47])[CH2:42][CH:43]([CH3:45])[CH3:44])=[O:39])([CH3:36])([CH3:35])[CH3:34].Cl.CN(C)CCCN=C=NCC>ClCCl>[C:33]([O:37][C:38]([NH:40][C@H:41]([C:46]([N:11]1[C@@H:7]([C:6]#[C:5][Si:2]([CH3:3])([CH3:4])[CH3:1])[CH2:8][CH2:9][C@H:10]1[C:12]([O:14][CH3:15])=[O:13])=[O:47])[CH2:42][CH:43]([CH3:44])[CH3:45])=[O:39])([CH3:35])([CH3:36])[CH3:34]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 218852-DimethylaminopyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12373896N-Boc-L-Leucine HydrateHCID 16090847methyl (5R)-5-((trimethylsilyl)ethynyl)-L-prolinate

Product 1

HCID 66757129methyl N-(tert-butoxycarbonyl)-L-leucyl-(5R)-5-((trimethylsilyl)ethynyl)-L-prolinate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl (5R)-5-((trimethylsilyl)ethynyl)-L-prolinate (1.6 grams, 7.48 mmol), dimethylaminopyridine (913 mg, 7.48 mmol), N-methylmorpholine (1.23 mL, 11.22 mmol), and N-(tert-butoxycabonyl)-L-leucine monohydrate (2.24 g, 8.98 mmol) in dichloromethane (30 mL) at room temperature was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.72 g, 8.98 mmol). The resulting mixture was stirred 16 hours at room temperature, and partitioned between ethyl acetate (200 mL) and 1 M HCl (200 mL). The aqueous layer was further extracted with ethyl acetate (200 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated. The residue was chromatographed with a Biotage 40 M cartridge with 40% ethyl acetate/hexane provide the titled compound. MS (DCI/NH3) m/e 439 (M+H)+.

Workup

  1. custompartitioned between ethyl acetate (200 mL) and 1 M HCl (200 mL)
  2. extractionThe aqueous layer was further extracted with ethyl acetate (200 mL)
  3. dry with materialThe combined organic layers were dried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed with a Biotage 40 M cartridge with 40% ethyl acetate/hexane

Sources & evidence

ORD record
ord-44adff9d7da642bba0c200d909d57559
Source dataset
uspto-grants-2007_07
Patent number
US07238724B2

Reaction notes

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