Triethylamine → HCID 178525393, compound

HRID 1634583Notes

Reaction equation

HRID 1634583 reaction equation
[H-].[Na+].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:10]2[CH:14]=[C:13]([CH2:15][CH2:16][CH2:17][CH2:18][OH:19])[N:12]=[CH:11]2)C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]2[CH:46]([N:47]3[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]3)[C:41]3=[N:42][CH:43]=[CH:44][CH:45]=[C:40]3[CH2:39][CH2:38][C:37]=2[CH:53]=1.C(N(CC)CC)C.Cl[C:62](Cl)([O:64]C(=O)OC(Cl)(Cl)Cl)Cl>O1CCCC1.ClCCl>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]2[CH:46]([N:47]3[CH2:48][CH2:49][N:50]([C:62]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][C:13]4[N:12]=[CH:11][NH:10][CH:14]=4)=[O:64])[CH2:51][CH2:52]3)[C:41]3=[N:42][CH:43]=[CH:44][CH:45]=[C:40]3[CH2:39][CH2:38][C:37]=2[CH:53]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 94429TriphosgeneHCID 5255691HCID 5255691, compoundHCID 11596091HCID 11596091, compound

Product 1

HCID 178525393HCID 178525393, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of sodium hydride (200 mg of 60% dispersion; 5.0 mmol) in dry tetrahydrofuran (25 mL), was added portionwise alcohol hydrochloride (4) (1.05 g; 2.5 mmol) over a period of 10 min. The resultant suspension was stirred at room temperature for 3.5 h. The piperazine derivative (8) (706 mg; 2.25 mmol) was added, the mixture was diluted with dry tetrahydrofuran (25 mL), and the resultant suspension allowed to stir overnight at room temperature. Triethylamine (0.35 mL; 2.5 mmol) was added, followed by the addition over about 4 min. of a solution of triphosgene (252 mg; 0.849 mmol) in dry dichloromethane (2.5 mL) (mild exotherm). The resultant suspension was stirred at room temperature for 6 h; then the solids were filtered and washed with ethyl acetate. The filtrate and washings were combined, and solvent removed under reduced pressure. Chromatography of the residue on silica gel, eluting with a gradient of ethyl acetate-methanol (98:2→95:5), yielded the title tritylated product (31) as a white glassy foam. ESIMS: 722 (MH+; 85%); 243 (Ph3C+; 100%). [A more polar fraction corresponding to symmetrical urea (30) was also isolated.]

Workup

  1. filtrationthen the solids were filtered
  2. washwashed with ethyl acetate
  3. customsolvent removed under reduced pressure
  4. washChromatography of the residue on silica gel, eluting with a gradient of ethyl acetate-methanol (98:2→95:5)

Sources & evidence

ORD record
ord-b89980c39028404e9ad96d386a8acc9b
Source dataset
uspto-grants-2003_01
Patent number
US06506756B2

Reaction notes

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