4-Methylmorpholine → N-[(1,1-dimethylethoxy)carbonyl]-2,6-dimethyl-O-[(phenylmethoxy)carbonyl]-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide

HRID 2291752Notes

Reaction equation

HRID 2291752 reaction equation
[CH3:1][C:2]([CH3:36])([O:4][C:5]([NH:7][C@H:8]([C:19]([NH:21][C@@H:22]([C:24]([NH:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:25])[CH3:23])=[O:20])[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([OH:17])=[CH:12][C:11]=1[CH3:18])=[O:6])[CH3:3].CN1CCOCC1.[CH2:44]([O:51][C:52](Cl)=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.CCCCCC>C(Cl)Cl>[CH3:36][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([C:19]([NH:21][C@@H:22]([C:24]([NH:26][CH2:27][CH2:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:25])[CH3:23])=[O:20])[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([O:17][C:52]([O:51][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:53])=[CH:12][C:11]=1[CH3:18])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 8058HexaneHCID 10387Benzyl chloroformate2×HCID 13656661N-[(1,1-dimethylethoxy)carbonyl]-2,6-dimethyl-tyrosyl-N-(3-phenylpropyl)-D-alaninamide

Product 1

HCID 14373532N-[(1,1-dimethylethoxy)carbonyl]-2,6-dimethyl-O-[(phenylmethoxy)carbonyl]-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamideYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To N[(1,1-dimethylethoxy)carbonyl]-2,6-dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide (1.0 g, 2.0 mmol) dissolved in 75 ml of CH2Cl2 and cooled to -20° C. was added 264 mg (0.3 mmol) of N-methylmorpholine. The reaction was then cooled to -78° C. and maintained under an argon atmosphere. Benzylchloroformate (445 mg, 2.5 mmol) was then added to the stirred reaction mixture. The reaction was allowed to slowly warm to room temperature an stir overnight. The mixture was then filtered and the filtrate diluted with CH2CL2 (150 ml). This filtrate was washed 3 times with 75 ml aliquots of 0.5N KHSO4 and once with 75 ml of brine before it was dried over Na2SO4. The organic layer was then stripped of all solvent under reduced pressure to yield a pale yellow solid which by TLC was a mixture of product and starting material. This material was redissolved in 40 ml of CH 2 CL2 and then retreated with N-methylmorpholine and benzylchloroformate in a manner identical to the reaction disclosed above. This second reaction was worked up as described for the original reaction yield a pale yellow solid which was then triterated with hexane containing 5% diethylether to give 1.24 g of the titled product.

Workup

  1. temperatureThe reaction was then cooled to -78° C.
  2. temperaturemaintained under an argon atmosphere
  3. temperatureto slowly warm to room temperature an stir overnight
  4. filtrationThe mixture was then filtered
  5. additionthe filtrate diluted with CH2CL2 (150 ml)
  6. washThis filtrate was washed 3 times with 75 ml aliquots of 0.5N KHSO4
  7. dry with materialonce with 75 ml of brine before it was dried over Na2SO4
  8. customto yield a pale yellow solid which by TLC
  9. additiona mixture of product
  10. dissolutionThis material was redissolved in 40 ml of CH 2 CL2
  11. customThis second reaction
  12. customas described for the original reaction
  13. customyield a pale yellow solid which

Sources & evidence

ORD record
ord-09ca0d5564694a3582fd19fb698febe1
Source dataset
uspto-grants-1989_01
Patent number
US04797470

Reaction notes

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