Triethylamine → HCID 18462057, compound

HRID 2303976Notes

Reaction equation

HRID 2303976 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][C:11]([OH:13])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[NH2:24][C:25]1[C:34]2[CH2:33][NH:32][CH2:31][CH2:30][C:29]=2[N:28]=[C:27]2[CH2:35][CH2:36][CH2:37][CH2:38][C:26]=12.C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>O1CCCC1.O.C(OCC)(=O)C>[NH2:24][C:25]1[C:34]2[CH2:33][N:32]([C:11](=[O:13])[CH2:10][CH:9]([C:4]3[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=3)[C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:31][CH2:30][C:29]=2[N:28]=[C:27]2[CH2:35][CH2:36][CH2:37][CH2:38][C:26]=12

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 15524260HCID 15524260, compoundHCID 17818832HCID 17818832, compound

Product 1

HCID 18462057HCID 18462057, compoundYield 168.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

108.08 g (0.300 mol) of (+)-3-(3,4-dichlorophenyl)-3-benzyloxycarbonylpropionic acid and 154.11 g (0.300 mol) of 10-amino-1,2,3,4,6,7,8,9-octahydrobenzo[b][1,6]-naphthyridine were suspended in 600 ml of tetrahydrofuran, and the solution was cooled to an internal temperature of 20° C. Then 127.50 g (0.126 mol) of triethylamine was added at an internal temperature of 30° C. or below over a period of 15 minutes and the solution was further cooled to an internal temperature of 20° C., after which 210.00 g (0.330 mol) of a 50% ethyl acetate solution of T3P was added dropwise at an internal temperature of 25° C. over a period of 20 minutes and the solution was stirred at this temperature for 2 hours. The internal temperature of the solution was lowered to 20° C., then 1,200 ml of water was added dropwise at an internal temperature of 25° C. over a period of 10 minutes, and the precipitated crystals were centrifugally filtered by a centrifuge and washed twice with 360 ml of a 1/2 mixture of THF and water to obtain 271.48 g (100% yield) of the title compound.

Workup

  1. temperaturethe solution was further cooled to an internal temperature of 20° C.
  2. customwas lowered to 20° C.
  3. filtrationthe precipitated crystals were centrifugally filtered by a centrifuge
  4. washwashed twice with 360 ml of a 1/2 mixture of THF and water

Sources & evidence

ORD record
ord-c103adefadc9444f876360c4029e7ef9
Source dataset
uspto-grants-2002_08
Patent number
US06433174B1

Reaction notes

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