4-Methylmorpholine → Boc-AlaAlaPro-OBzl

HRID 1458178Notes

Reaction equation

HRID 1458178 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:21])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:20])[C@H:17]([CH3:19])[NH2:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN1CCOCC1.[C:29]([NH:36][C@H:37]([C:39](O)=[O:40])[CH3:38])([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].C(ON1C2C(=CC=CC=2)CC(=C=O)C1OCC)C>C(Cl)Cl.O>[CH2:2]([O:9][C:10](=[O:21])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:20])[C@H:17]([CH3:19])[NH:18][C:39](=[O:40])[C@H:37]([CH3:38])[NH:36][C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 85082Tert-butoxycarbonylalanineHCID 13034412L-alanyl-L-proline, phenylmethyl ester, hydrochlorideHCID 867493291-Ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline

Product 1

HCID 15289361Boc-AlaAlaPro-OBzlYield 81.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

L-alanyl-L-proline benzyl ester hydrochloride (13.0 g, 41.6 mmol) was dissolved in methylene chloride (650 ml) under an argon atmosphere in a flask fitted with an over-head stirrer. N-methylmorpholine (4.8 ml, 43.6 mmol) was syringed into the solution and, after 5 minutes, Boc-L-alanine (7.9 g, 41.6 mmol) was added followed by 1-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (11.8 g, 47.8 mmol). The resulting solution was stirred at room temperature overnight. The reaction mixture was poured into a separatory funnel containing water (300 ml) and the layers separated. The aqueous layer was extracted with chloroform (200 ml) and the combined organic extracts were washed with 0.5N hydrochloric acid (3×200 ml), water (2×200 ml), saturated sodium bicarbonate (2×200 ml) and brine (200 ml). The organic layer was then dried over magnesium sulfate, filtered and concentrated on a rotary evaporator. Addition of ether-hexane gave crude Boc-L-alanyl-L-alanyl-L-proline benzyl ester which could be recrystallized from ethyl acetate-hexane to give the pure product (15.1 g) mp 124°-126° C.

Workup

  1. customfitted with an over-head stirrer
  2. additionThe reaction mixture was poured into a separatory funnel
  3. customthe layers separated
  4. extractionThe aqueous layer was extracted with chloroform (200 ml)
  5. washthe combined organic extracts were washed with 0.5N hydrochloric acid (3×200 ml), water (2×200 ml), saturated sodium bicarbonate (2×200 ml) and brine (200 ml)
  6. dry with materialThe organic layer was then dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated on a rotary evaporator
  9. additionAddition of ether-hexane
  10. customgave crude Boc-L-alanyl-L-alanyl-L-proline benzyl ester which
  11. customcould be recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-5bc1278c4a2a4e538a2b4850f28d6349
Source dataset
uspto-grants-1998_12
Patent number
US05849866

Reaction notes

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