4-Methylmorpholine → HCID 131718971, compound

HRID 1654588Notes

Reaction equation

HRID 1654588 reaction equation
[N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=O.[NH2:19][C@H:20]([C:31]([NH:33][C@H:34]([C:39]([NH:41][C@H:42]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:43][CH:44]([CH3:46])[CH3:45])=[O:40])[C:35]([CH3:38])([CH3:37])[CH3:36])=[O:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[N:1]1([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH:19][C@H:20]([C:31]([NH:33][C@H:34]([C:39]([NH:41][C@H:42]([C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:43][CH:44]([CH3:45])[CH3:46])=[O:40])[C:35]([CH3:37])([CH3:38])[CH3:36])=[O:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[NH:24][CH:23]=1)=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 101987Benzyloxycarbonyl-L-prolineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 131718972HCID 131718972, compound

Product 1

HCID 131718971HCID 131718971, compoundYield 89.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Z-Pro (2.18 g, 8.3 mmol) and Trp-Tle-Leu-OEt (prepared by catalytic hydrogenation of Z-Trp-Tle-Leu-OEt over palladium on charcoal) (3.47 g, 7.6 mmol), and NMM (0.92 mL) are dissolved in 35 mL DMF, cooled to 0° C., and treated with TBTU (2.66 g, 8.3 mmol). The reaction is stirred at 0° C. for 1 hour then removed from the ice bath and stirred at room temperature for 2 hours. The mixture is poured into 350 mL of a saturated solution of sodium bicarbonate which is then extracted with 350 mL of ethyl acetate. The combined organic extracts are washed with 350 mL of 1 M KHSO4, water and brine, and then dried over sodium sulfate. The solvents are removed and the residue chromatographed on silica gel (1.5% MeOH in chloroform) to give Z-Pro-Trp-Tle-Leu-OEt (Seq ID No: 7) (4.7 g). FABMS M+1 690

Workup

  1. customthen removed from the ice bath
  2. stirringstirred at room temperature for 2 hours
  3. additionThe mixture is poured into 350 mL of a saturated solution of sodium bicarbonate which
  4. extractionis then extracted with 350 mL of ethyl acetate
  5. washThe combined organic extracts are washed with 350 mL of 1 M KHSO4, water and brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvents are removed
  8. customthe residue chromatographed on silica gel (1.5% MeOH in chloroform)

Sources & evidence

ORD record
ord-4c7a8abc69fb4bdcab139d2bcb151203
Source dataset
uspto-grants-1995_04
Patent number
US05407916

Reaction notes

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