Hydrochloric Acid → (S)-[1-[[[[4-[[[4,5-Bis(phenylmethoxy)-2-pyridinyl]carbonyl]amino]-2,3-dioxo-1-piperazinyl]sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester

HRID 1252622Notes

Reaction equation

HRID 1252622 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][C@H:12]2[CH2:15][NH:14][C:13]2=[O:16])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[S:18]([N:21]=[C:22]=[O:23])(=[O:20])=[O:19].C(N(CC)CC)C.[O:31]=[C:32]1[C:37](=[O:38])[NH:36][CH2:35][CH2:34][N:33]1[NH:39][C:40]([C:42]1[CH:47]=[C:46]([O:48][CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:45]([O:56][CH2:57][C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)=[CH:44][N:43]=1)=[O:41].CN([Si](C)(C)C)C(=O)C(F)(F)F.Cl>C(OCC)(=O)C.[Cl-].[Na+].O>[C:50]1([CH2:49][O:48][C:46]2[C:45]([O:56][CH2:57][C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)=[CH:44][N:43]=[C:42]([C:40]([NH:39][N:33]3[CH2:34][CH2:35][N:36]([S:18]([NH:21][C:22]([N:14]4[CH2:15][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:7][C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[C:13]4=[O:16])=[O:23])(=[O:20])=[O:19])[C:37](=[O:38])[C:32]3=[O:31])=[O:41])[CH:47]=2)[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 32510N-methyl-N-(trimethylsilyl)trifluoroacetamideHCID 70918Chlorosulfonyl isocyanateHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 14182508N-(2,3-Dioxo-1-piperazinyl)-4,5-bis(phenylmethoxy)-2-pyridinecarboxamide

Product 1

HCID 86742167(S)-[1-[[[[4-[[[4,5-Bis(phenylmethoxy)-2-pyridinyl]carbonyl]amino]-2,3-dioxo-1-piperazinyl]sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (2.02 g, 9.18 mmol) in 130 ml of ethyl acetate, chlorosulfonyl isocyanate (1.43 g, 10 mmol) was added, and, after stirring for one hour, triethylamine (2.79 g, 27.54 mmol) was added at 0° C. To this mixture, a prestirred solution (1.5 hours) of N-(2,3-dioxo-1-piperazinyl)-4,5-bis(phenylmethoxy)-2-pyridinecarboxamide (4.10 g, 9.18 mmol) and N-methyl-N-(trimethylsilyl)trifluoroacetamide (5.4 g, 27.54 mmol) in 150 ml of ethyl acetate was added. After stirring overnight at room temperature, 220 ml of ice water was added and the pH was adjusted to 2 (from 10.3) with 3N hydrochloric acid. When the separated organic phase was treated with brine, the title compound precipitated and was filtered, washed with water and dried in vacuo, yielding 5.35 g. When 2.5 g of this material was triturated for one hour with a mixture of 25 ml of water and 37.5 ml of acetone at pH 6.3, 2.12 g of the title compound was obtained.

Workup

  1. additionwas added
  2. stirringAfter stirring overnight at room temperature
  3. customthe title compound precipitated
  4. filtrationwas filtered
  5. washwashed with water
  6. customdried in vacuo
  7. customyielding 5.35 g
  8. customWhen 2.5 g of this material was triturated for one hour with a mixture of 25 ml of water and 37.5 ml of acetone at pH 6.3, 2.12 g of the title compound
  9. customwas obtained

Sources & evidence

ORD record
ord-11367a6b089a4cdd93afa6b451a01272
Source dataset
uspto-grants-1988_05
Patent number
US04743685

Reaction notes

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