Bromoacetonitrile → (R)-tert-butyl 4-(((S)-5-((tert-butoxycarbonyl)amino)-6-(cyanomethoxy)-6-oxohexyl)carbamoyl)thiazolidine-3-carboxylate

HRID 1482365Notes

Reaction equation

HRID 1482365 reaction equation
Br[CH2:2][C:3]#[N:4].C(N(CC)C(C)C)(C)C.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31]([C@@H:33]1[CH2:37][S:36][CH2:35][N:34]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:32])[C:23]([OH:25])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15]>C(#N)C>[C:14]([O:18][C:19]([NH:21][C@H:22]([C:23]([O:25][CH2:2][C:3]#[N:4])=[O:24])[CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:31]([C@@H:33]1[CH2:37][S:36][CH2:35][N:34]1[C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])=[O:32])=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 81531DiisopropylethylamineHCID 89668375(S)-2-((tert-butoxycarbonyl)amino)-6-((R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxamido)hexanoic acid

Product 1

HCID 89668744(R)-tert-butyl 4-(((S)-5-((tert-butoxycarbonyl)amino)-6-(cyanomethoxy)-6-oxohexyl)carbamoyl)thiazolidine-3-carboxylateYield 99.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Bromoacetonitrile (57 μl, 0.845 mmol) and N,N-diisopropylethylamine (147 μl, 0.845 mmol) were added to a solution of (S)-2-((tert-butoxycarbonyl)amino)-6-((R)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxamido)hexanoic acid (Compound tk82) (130 mg, 0.282 mmol) in acetonitrile (5 ml), and the reaction solution was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure using an evaporator, and the residue was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate) to afford (R)-tert-butyl 4-(((S)-5-((tert-butoxycarbonyl)amino)-6-(cyanomethoxy)-6-oxohexyl)carbamoyl)thiazolidine-3-carboxylate (Compound tk83) (140 mg, 99%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customan evaporator
  3. customthe residue was purified by normal-phase silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-fa216b0193c0417888bb99fcaf6598e1
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

Loading…