N-[tert-butoxycarbonyl]-L-serine → HCID 11490014, compound

HRID 375723Notes

Reaction equation

HRID 375723 reaction equation
[NH2:1][C@H:2]1[CH2:13][O:12][C:11](=[O:14])[C:10]2[C:15]([CH3:35])=[C:16]([O:27][Si](C(C)(C)C)(C)C)[CH:17]=[C:18]([O:19][Si](C(C)(C)C)(C)C)[C:9]=2[CH2:8][S:7][CH2:6][C@@H:5]([C:36]([O:38][CH3:39])=[O:37])[NH:4][C:3]1=[O:40].[C:41]([O:45][C:46]([NH:48][C@H:49]([C:52](O)=[O:53])[CH2:50][OH:51])=[O:47])([CH3:44])([CH3:43])[CH3:42].Cl.CN(CCCN=C=NCC)C>C(#N)C.C(OCC)(=O)C>[C:41]([O:45][C:46]([NH:48][C@@H:49]([CH2:52][OH:53])[C:50]([NH:1][C@H:2]1[CH2:13][O:12][C:11](=[O:14])[C:10]2[C:15]([CH3:35])=[C:16]([OH:27])[CH:17]=[C:18]([OH:19])[C:9]=2[CH2:8][S:7][CH2:6][C@@H:5]([C:36]([O:38][CH3:39])=[O:37])[NH:4][C:3]1=[O:40])=[O:51])=[O:47])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 3

HCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 56607844HCID 56607844, compound

Product 1

HCID 11490014HCID 11490014, compoundYield 38.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 61 mg of methyl (4R, 7S)-7-amino-12,14-bis(tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8,10-octahydro-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate and 21 mg N-(tert-butoxycarbonyl)-L-serine in 2 ml of acetonitrile, cooled to 0° C., were added 20 mg of N-(dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride. The mixture was stirred at 0° C. for 4 hours, then diluted with 30 ml of ethyl acetate, and washed successively with 0.5N hydrochloric acid, water, 5% sodium bicarbonate solution, and with brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was dissolved in 2 ml of methanol, 20 mg of ammonium fluoride were added, and the mixture was stirred for 30 minutes at room temperature. The mixture was diluted with 40 ml of ethyl acetate and washed with 30 ml of water. The organic layer was dried over sodium sulfate, and the solvent was evaporated in vacuo. The solid residue was triturated with 2 ml of ether, then hexane was added, and the white solid was isolated by filtration to give 22 mg of methyl (4R, 7S)-7-[(S)-2-(1-tert-butoxyformamido)-3-hydroxypropionylamino]-1,3,4,5,6,7,8,10-octahydro-12,14-dihydroxy-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate.

Workup

  1. washwashed successively with 0.5N hydrochloric acid, water, 5% sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in 2 ml of methanol
  5. addition20 mg of ammonium fluoride were added
  6. stirringthe mixture was stirred for 30 minutes at room temperature
  7. additionThe mixture was diluted with 40 ml of ethyl acetate
  8. washwashed with 30 ml of water
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. customthe solvent was evaporated in vacuo
  11. customThe solid residue was triturated with 2 ml of ether
  12. additionhexane was added
  13. customthe white solid was isolated by filtration

Sources & evidence

ORD record
ord-2ef36b9f367b45eb9a7abb022d11f0cb
Source dataset
uspto-grants-1996_01
Patent number
US05486466

Reaction notes

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