Ethylmorpholine → N-(N'-(Boc)-glutaminyl-serinyl)leucine benzyl ester

HRID 276768Notes

Reaction equation

HRID 276768 reaction equation
Cl.[CH2:2]([O:9][C:10](=[O:23])[C@H:11]([CH2:19][CH:20]([CH3:22])[CH3:21])[NH:12][C:13](=[O:18])[C@H:14]([CH2:16][OH:17])[NH2:15])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C=CC2N([OH:33])N=NC=2C=1.[C:34]([NH:41][C@H:42](C(O)=O)[CH2:43][CH2:44][C:45](=O)[NH2:46])([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C(N1C[CH2:57][O:56]CC1)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[CH2:2]([O:9][C:10](=[O:23])[C@H:11]([CH2:19][CH:20]([CH3:21])[CH3:22])[NH:12][C:13](=[O:18])[C@H:14]([CH2:16][OH:17])[NH:15][C:57](=[O:56])[C@H:45]([CH2:44][CH2:43][C:42](=[O:33])[NH:41][C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[NH2:46])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 5

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 83687L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69994837N-(serinyl)leucine benzyl ester hydrochloride

Product 1

HCID 69995241N-(N'-(Boc)-glutaminyl-serinyl)leucine benzyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-(serinyl)leucine benzyl ester hydrochloride (350 g) (prepared as described in Step 1), HOBt (157.7 g) and N-Boc-L-glutamine (262.5 g) were slurried in DMF (2.5 L) and the mixture was cooled to 0° C. N-Ethylmorpholine (245.5 g) and EDC.HCl (214 g) were added and the mixture was aged at 0° C. for 2.5 hours. Water (14.7 L) was added over 20 minutes and the white slurry aged at 0° C. for 1 hour. The product collected by filtration and washed with water (3.2 L). The cake was dried in the fume-hood overnight. The isolated N-BOC-Gln-Ser-Leu-OBn, which contained DMF and HOBt, was combined with a second batch of identical size, and swished in water (12 L) at 20° C. for 1 hour. The product was collected by filtration, washed with water (2.5 L) and air-dried in a fume-hood over the weekend. The batch was dried in vacuo, at 42° C., with a nitrogen bleed.

Workup

  1. waitthe white slurry aged at 0° C. for 1 hour
  2. filtrationThe product collected by filtration
  3. washwashed with water (3.2 L)
  4. customThe cake was dried in the fume-hood overnight
  5. waitswished in water (12 L) at 20° C. for 1 hour
  6. filtrationThe product was collected by filtration
  7. washwashed with water (2.5 L)
  8. customair-dried in a fume-hood over the weekend
  9. customThe batch was dried in vacuo, at 42° C., with a nitrogen

Sources & evidence

ORD record
ord-58d6ebbb5dfd4fac93f06568b8096a47
Source dataset
uspto-grants-2002_03
Patent number
US06355611B1

Reaction notes

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