Trimethylsilyl cyanide → HCID 13521702, compound

HRID 2121002Notes

Reaction equation

HRID 2121002 reaction equation
ClC1C=CC=CC=1[NH:8][CH2:9][C:10]([OH:12])=[O:11].[Cl:13][C:14]1[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=1[CH:16]([NH:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:17]#[N:18].[Cl:37][C:38]1[CH:45]=[C:44]([Cl:46])[CH:43]=[C:40]([CH:41]=[O:42])[C:39]=1[OH:47].[NH2:48][C@H:49]([C:54]([OH:56])=[O:55])[C:50]([CH3:53])([CH3:52])[CH3:51].[C:57]([O:61][C@H:62]([CH3:68])[C@@H:63]([C:65]([OH:67])=[O:66])[NH2:64])([CH3:60])([CH3:59])[CH3:58].NCC(O)=O.C[Si](C#N)(C)C>C1(C)C=CC=CC=1.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].CCOCC>[Cl:37][C:38]1[CH:45]=[C:44]([Cl:46])[CH:43]=[C:40]([CH:41]=[O:42])[C:39]=1[OH:47].[NH2:48][C@H:49]([C:54]([OH:56])=[O:55])[C:50]([CH3:53])([CH3:52])[CH3:51].[C:57]([O:61][C@H:62]([CH3:68])[C@@H:63]([C:65]([OH:67])=[O:66])[NH2:64])([CH3:60])([CH3:58])[CH3:59].[CH3:14][O:12][C:10](=[O:11])[CH2:9][NH2:8].[Cl:13][C:14]1[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=1[CH:16]([NH:19][CH:20]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:17]#[N:18]

Participants

9

Reactant 4

HCID 82115Trimethylsilyl cyanideHCID 247831D-(2-Chlorophenyl)glycineHCID 13521702HCID 13521702, compoundHCID 131724342HCID 131724342, compound

Product 2

HCID 13521702HCID 13521702, compoundHCID 131724341HCID 131724341, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

The following is an example of a solution phase catalyzed reaction to synthesize 2-chlorophenyl glycine. Screening of the above library determined that a preferred catalyst for the formation of N-(2-chloro-a-cyanobenzyl)benzhydrylamine was 3,5-Dichlorosalicylaldehyde-tert-Leucine-(O-tert-Butyl)Threonine-Glycine. 3,5-Dichlorosalicylaldehyde-tert-Leucine-(O-tert-Butyl)Threonine-Glycine methyl ester was synthesized using standard solid-phase synthesis techniques and was added (53.3 mg, 0.1 mmol) under a nitrogen atmosphere to a solution of titanium tetraisopropoxide (29.5 ul, 0.1 mmol) in toluene (2 ml), and the mixture was stirred for about 15 minutes. Ortho-chlorobenzylidenylbenzhydrylamine (306 mg, 1.0 mmol) was added and the mixture stirred until complete dissolution of the substrate (ca. 10 minutes). Trimethylsilylcyanide (267 ul, 2.0 mmol) was added to the solution and the resultant mixture was stirred for 48 hours. Addition of ether (2 ml, 5% water) followed by filtration through silica afforded a product that was predominantly the desired isomer contaminated with a small amount of starting material. Addition of hexanes to the ethereal solution afforded pure N-(2-chloro-a-cyanobenzyl)benzhydrylamine as white crystals. Analysis by HPLC indicated optical purity of >99%.

Workup

  1. customreaction
  2. customsolid-phase synthesis techniques
  3. additionOrtho-chlorobenzylidenylbenzhydrylamine (306 mg, 1.0 mmol) was added
  4. stirringthe mixture stirred until complete dissolution of the substrate (ca. 10 minutes)
  5. filtrationfollowed by filtration through silica
  6. customafforded a product that

Sources & evidence

ORD record
ord-d828bf5350344ca8979612e41b33de9a
Source dataset
uspto-grants-2004_02
Patent number
US06693168B1

Reaction notes

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