Dichloromethane → Dicyclopropyl{5-[3-(morpholin-4-yl)-5-nitrophenyl]-1,3-thiazol-2-yl}methanol

HRID 410533Notes

Reaction equation

HRID 410533 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([CH:12]2[CH2:14][CH2:13]2)([CH:9]2[CH2:11][CH2:10]2)[OH:8])=[N:4][CH:3]=1.[N+:15]([C:18]1[CH:19]=[C:20]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=1)([O-:17])=[O:16].C([O-])([O-])=O.[Na+].[Na+].ClCCl>COCCOC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:9]1([C:7]([CH:12]2[CH2:14][CH2:13]2)([C:5]2[S:6][C:2]([C:22]3[CH:23]=[C:18]([N+:15]([O-:17])=[O:16])[CH:19]=[C:20]([N:33]4[CH2:38][CH2:37][O:36][CH2:35][CH2:34]4)[CH:21]=3)=[CH:3][N:4]=2)[OH:8])[CH2:11][CH2:10]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 672568704-(3-Nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)morpholineHCID 67429273(5-Bromothiazol-2-yl)dicyclopropylmethanol

Product 1

HCID 67258049Dicyclopropyl{5-[3-(morpholin-4-yl)-5-nitrophenyl]-1,3-thiazol-2-yl}methanolYield 68.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product of Step 2 (239 mg, 0.872 mmol), crude product of Step 3 (320 mg, ˜0.96 mmol), Pd(dppf)Cl2 (31.9 mg, 0.044 mmol) and Na2CO3 (aq) (2.0 M, 1.3 mL, 2.6 mmol) in DME (4.4 mL) was irradiated to 130° C. in the microwave for 35 minutes. The reaction mixture was filtered through a celite pad with dichloromethane and the filtrate was concentrated. The residue was purified twice by chromatography on silica gel (0-100% ethyl acetate in hexanes then 0-60% dichloromethane in ethyl acetate) to give the desired dicyclopropyl{5-[3-(morpholin-4-yl)-5-nitrophenyl]-1,3-thiazol-2-yl}methanol (239 mg, 0.595 mmol, 68% yield) as a yellow solid. MS APCI: [M-OH]+ m/z 385.1.

Workup

  1. filtrationThe reaction mixture was filtered through a celite pad with dichloromethane
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified twice by chromatography on silica gel (0-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5fba027e6c0f4fa39fb0fdc283a46111
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…