Triethylamine → N,N'-Dicyclohexyl-1,2-ethanediamine

HRID 18693

Reaction equation

HRID 18693 reaction equation
[NH2:1][CH:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]12.[CH2:16](N(CC)CC)C.[NH2:23][C:24]1[S:25][CH:26]=[C:27](/[C:29](=[N:43]/[O:44]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)/[C:30](O[C:33]2[C:38]3N=C(S)S[C:37]=3[CH:36]=[CH:35][CH:34]=2)=[O:31])[N:28]=1>O1CCCC1.O>[CH:5]1([NH:4][CH2:14][CH2:2][NH:1][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:6][CH2:9][CH2:10][CH2:16][CH2:11]1.[NH2:23][C:24]1[S:25][CH:26]=[C:27](/[C:29](=[N:43]/[OH:44])/[C:30]([NH:1][C@@H:2]2[C:14](=[O:15])[N:4]3[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]23)=[O:31])[N:28]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 128180067-Amino-3vinyl-3-cephem-4-carboxylic acidHCID 178508500HCID 178508500, compound

Product 2

HCID 273886N,N'-Dicyclohexyl-1,2-ethanediamineHCID 6915944Cefdinir

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
32 °C

Procedure

To a chilled suspension of 7-amino-3-vinyl-3-cephem-4-carboxylic acid (50 gm) in a mixture of tetrahydrofuran (250 ml) and water (31.5 ml), triethylamine (45 gm) was added drop-wise at 20±2° C. over 30-45 minutes. 2-mercaptobenzothiazolyl (Z)-(2-aminothiazol-4-yl)-2-(trityloxyimino)acetate (130 gm) was added to the clear solution and the resulting mixture was stirred at 32±2° C. for 4-6 hours. The reaction was monitored by HPLC. After the completion of reaction, THF was completely removed under vacuum at 28-30° C. To the concentrated mass, acetone (300 mL) was added and stirred at 30° C., 1:1 Hydrochloric acid (200 mL) was added and the temperature was raised to 63-64° C. At this temperature, it was refluxed for about 35 min and then cold acetone of 1.8 Liter dumped to the reaction mass to bring down the temperature to 30° C., EDTA (0.5 g) was added and stirred for 10 min at 30-35° C., pH of the solution was adjusted to 2.5 using Triethyl amine (100 mL) at 30-35° C. To the reaction mixture hot solution of N,N′-Dicyclohexylethylenediamine (DDA) 40.0 g in Isopropyl alcohol (100 mL) was added slowly to adjust the pH of the solution 5.5 and stirred for 1.0 hour at 30-35° C. The precipitated material was filtered, washed with acetone and dried under vacuum at ˜40° C. to get N,N′-Dicyclohexylethylenediamine salt of 7β-[2-(2-amino-4-thiazolyl)-2-(Z-hydroxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid. Step-ii

Workup

  1. additionwas added drop-wise at 20±2° C. over 30-45 minutes
  2. customwas completely removed under vacuum at 28-30° C
  3. additionTo the concentrated mass, acetone (300 mL) was added
  4. stirringstirred at 30° C.
  5. addition1:1 Hydrochloric acid (200 mL) was added
  6. temperaturethe temperature was raised to 63-64° C
  7. temperatureAt this temperature, it was refluxed for about 35 min
  8. customto 30° C.
  9. additionEDTA (0.5 g) was added
  10. stirringstirred for 10 min at 30-35° C.
  11. customwas adjusted to 2.5 using Triethyl amine (100 mL) at 30-35° C
  12. additionTo the reaction mixture hot solution of N,N′-Dicyclohexylethylenediamine (DDA) 40.0 g in Isopropyl alcohol (100 mL) was added slowly
  13. stirringstirred for 1.0 hour at 30-35° C
  14. filtrationThe precipitated material was filtered
  15. washwashed with acetone
  16. customdried under vacuum at ˜40° C.

Sources & evidence

ORD record
ord-4dfc3d44ec72461482ef153742ee358f
Source dataset
uspto-grants-2010_06
Patent number
US07741478B2

Linked notes

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