HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

1-(2,3,6-Trifluorophenyl)propan-2-one → Isopropyl 2-(Boc-amino)-5-oxo-4-(2,3,6-trifluorophenyl)hexanoate

HRID 706370
Notes
Print preview

Reaction equation

HRID 706370 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[CH2:10][C:11](=[O:13])[CH3:12].[C:14]([O:18][C:19]([NH:21][CH:22]([CH2:29]OS(C)(=O)=O)[C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].C(O[Li])(C)(C)C>CC(OC)(C)C.[Br-].[Zn+2].[Br-]>[C:14]([O:18][C:19]([NH:21][CH:22]([CH2:29][CH:10]([C:3]1[C:4]([F:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1])[C:11](=[O:13])[CH3:12])[C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 552746091-(2,3,6-Trifluorophenyl)propan-2-oneHCID 89815000isopropyl N-(tert-butoxycarbonyl)-O-(methylsulfonyl)serinateHCID 178506942HCID 178506942, compound

Product 1

HCID 89814841Isopropyl 2-(Boc-amino)-5-oxo-4-(2,3,6-trifluorophenyl)hexanoateYield 67.5%

Reagents, catalysts & solvents 2

HCID 10421208
Zinc bromide
Catalyst
HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 18 (195 g, 1.03 mol) in MTBE (1.8 L) was added zinc bromide (67 g, 0.30 mol) followed by 2 (390 g, 1.2 mol). tert-BuOLi (290 g, 3.6 mol) was then added in several portions while maintaining the reaction temperature below 40° C. The resulting mixture was stirred at 35° C. for 24 h and quenched into a mixture of 2 N HCl (5.6 L) and heptane (5 L) at 0° C. The organic layer was separated and washed with 5% aqueous NaHCO3 (5 L) twice. The resulting organic solution was concentrated under vacuum. The residue was dissolved in heptane (2 L) and the solution was concentrated again under vacuum. The resulting oil was dissolved in DMSO (2.5 L) and the solution was used in the next step without further purification. HPLC analysis indicated that the solution contained the desired product 19 (290 g, 67% yield) as the major component along with 5% of starting material 18. The analytically pure product 19 as one pair of diastereomers was isolated by chromatography on silica gel with ethyl acetate and heptane mixture as an eluant. HRMS: m/z calcd for C20H26F3NO5 418.1836 (M+H). found 418.1849.

Workup

  1. temperaturewhile maintaining the reaction temperature below 40° C
  2. customquenched into a mixture of 2 N HCl (5.6 L) and heptane (5 L) at 0° C
  3. customThe organic layer was separated
  4. washwashed with 5% aqueous NaHCO3 (5 L) twice
  5. concentrationThe resulting organic solution was concentrated under vacuum
  6. dissolutionThe residue was dissolved in heptane (2 L)
  7. concentrationthe solution was concentrated again under vacuum
  8. dissolutionThe resulting oil was dissolved in DMSO (2.5 L)
  9. customthe solution was used in the next step without further purification

Sources & evidence

ORD record
ord-1530790ab55346a49ee807be473629e0
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09174989B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes