Trimethylsilyl cyanide → [5-(2-Amino-1-hydroxy-ethyl)-thiazol-2-yl]-carbamic acid tert-butyl ester

HRID 1818955Notes

Reaction equation

HRID 1818955 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[S:9][C:10]([CH:13]=[O:14])=[CH:11][N:12]=1)([CH3:4])([CH3:3])[CH3:2].C[Si]([C:20]#[N:21])(C)C>ClCCl.[Zn+2].[I-].[I-]>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[S:9][C:10]([CH:13]([OH:14])[CH2:20][NH2:21])=[CH:11][N:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 82115Trimethylsilyl cyanideHCID 53393345tert-butyl N-(5-formyl-1,3-thiazol-2-yl)carbamate

Product 1

HCID 86603181[5-(2-Amino-1-hydroxy-ethyl)-thiazol-2-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 62.3 (4.5 mmol) in dichloromethane is added trimethylsilyl cyanide (“TMSCN”; 2.1 equivalents) and ZnI2 (10% mol). After stirring at room temperature overnight, the reaction is concentrated under vacuum. The crude cyanohydrin is dissolved in THF and treated with AlH3 (2.2 equivalents of a 0.5 M solution in THF). After stirring for 15 minutes, the reaction is quenched with the addition of saturated aqueous Na2SO4, is filtered through a pad of Celite, is dried and concentrated. Purification by flash column chromatography on silica gel (10% 7.0 M NH3/MeOH in dichloromethane) provides [5-(2-amino-1-hydroxy-ethyl)-thiazol-2-yl]-carbamic acid tert-butyl ester (compound 62.4).

Workup

  1. concentrationthe reaction is concentrated under vacuum
  2. dissolutionThe crude cyanohydrin is dissolved in THF
  3. additiontreated with AlH3 (2.2 equivalents of a 0.5 M solution in THF)
  4. stirringAfter stirring for 15 minutes
  5. customthe reaction is quenched with the addition of saturated aqueous Na2SO4
  6. filtrationis filtered through a pad of Celite
  7. customis dried
  8. concentrationconcentrated
  9. customPurification by flash column chromatography on silica gel (10% 7.0 M NH3/MeOH in dichloromethane)

Sources & evidence

ORD record
ord-6aa517b5c27e43b18952cf542a475dbc
Source dataset
uspto-grants-2009_10
Patent number
US07601725B2

Reaction notes

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