Nitrogen → HCID 51348522, compound

HRID 454966Notes

Reaction equation

HRID 454966 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:11][C:12]([C@H:14]2[CH2:16][C@@H:15]2[C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:9][OH:10])=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].B(O)(O)[C:31]1[CH:32]=[CH:33][C:34]([CH3:37])=[CH:35][CH:36]=1.N#N.[OH-].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:10][CH2:9][C@H:8]([NH:11][C:12]([C@H:14]1[CH2:16][C@@H:15]1[C:17]1[S:18][CH:19]=[CH:20][CH:21]=1)=[O:13])[C:5]1[CH:6]=[CH:7][C:2]([C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)=[CH:3][CH:4]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 79799Tolylboronic acidHCID 67430041HCID 67430041, compound

Product 1

HCID 51348522HCID 51348522, compoundYield 47.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic acid [(R)-1-(4-bromo-phenyl)-2-hydroxy-ethyl]-amide (560 mg, 1.53 mmol), K3PO4 (650 mg, 3.0 mmol)) and p-tolylboronic acid (310 mg, 2.3 mmol) in DME/H2O (3/1, 2 ml) was passed through N2 and then Pd(PPh3)4 (178 mg, 0.153 mmol) added. The mixture was stirred in a sealed tube at 85° C. for 1.5 h. The reaction mixture was poured 1N NaOH and extracted with EtOAc (3×). The combined EtOAc layer was dried over MgSO4. After removal of the solvent, the residue was subjected to silica column (50% EtOAc in DCM and then 10% MeOH in DCM). The product obtained was further purified by crystallization (iPrOH/EtOAc) and Prep HPLC to give the titled compound (275 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.6 (d, J=8.1 Hz, 2H), 7.5 (d, J=7.8 Hz, 2H), 7.4 (d, J=8.1 Hz, 2H), 7.2 (d, J=7.6 Hz, 2H), 7.1 (t, J=5.4 Hz, 1H), 6.8-7.0 (m, 2H), 5.0 (dd, J=5.4, 1.9 Hz, 1H), 3.7-3.8 (m, 2H), 2.5-2.7 (m, 1H), 2.4 (s, 3H), 2.1 (t, J=8.7 Hz, 1H), 1.4-1.6 (m, 1H), 1.2 (ddd, 1H). LRMS (ESI)=378, [(M+1)+ calcd for C23H24NO2S 377.5].

Workup

  1. extractionextracted with EtOAc (3×)
  2. dry with materialThe combined EtOAc layer was dried over MgSO4
  3. customAfter removal of the solvent
  4. customThe product obtained
  5. customwas further purified by crystallization (iPrOH/EtOAc) and Prep HPLC

Sources & evidence

ORD record
ord-4f2d7f9e2e5a4fd3b8f199a44f58b4fb
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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