Hydrochloric Acid → HCID 58104611, compound

HRID 1671389Notes

Reaction equation

HRID 1671389 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([C@H:13]([CH:15]2[CH2:20][CH2:19][C:18]([F:22])([F:21])[CH2:17][CH2:16]2)[OH:14])[CH2:9]1)=O)(C)(C)C.C1C=NC2C3N=CC=CC=3C=CC=2C=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:43][C:44]1[CH:49]=[C:48](I)[CH:47]=[C:46]([Cl:51])[CH:45]=1.C1(C)C=CC=CC=1.Cl.CCO>[Cu]I>[Cl:43][C:44]1[CH:49]=[C:48]([CH:47]=[C:46]([Cl:51])[CH:45]=1)[O:14][CH:13]([CH:15]1[CH2:16][CH2:17][C:18]([F:21])([F:22])[CH2:19][CH2:20]1)[CH:10]1[CH2:11][CH2:12][NH:8][CH2:9]1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1140TolueneHCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 764241,3-Dichloro-5-iodobenzeneHCID 66892198HCID 66892198, compound

Product 1

HCID 58104611HCID 58104611, compound

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
105 °C

Procedure

(R)-3-[(S)-(4,4-Difluorocyclohexyl)hydroxymethyl]pyrrolidine-1-carboxylic acid t-butyl ester (44.0 mg, 138 μmmol), copper(I) iodide (7.9 mg, 41 μmmol), o-phenanthroline (15 mg, 83 μmmol) and cesium carbonate (89.8 mg, 276 μmmol) were combined. 1,3-Dichloro-5-iodobenzene (75.2 mg, 276 μmmol) was added, followed by the addition of toluene (220 μL, 2.1 mmol). Air was bubbled through the mixture, the vessel was sealed, and the mixture was heated at 105° C. for 48 hours. The mixture was filtered, rinsed with DCM, and concentrated. The crude material was treated with 1.25M HCl in EtOH (5.8 mL, 7.2 mmol) and stirred overnight. The mixture was concentrated, redissolved in 1:1 AcOH:H2O and purified by preparative HPLC to yield the title compound as a mono-TFA salt (1.5 mg, 96% purity). MS m/z: [M+H]+ calcd for C17H21Cl2F2NO, 364.10; found 364.0.

Workup

  1. customAir was bubbled through the mixture
  2. customthe vessel was sealed
  3. filtrationThe mixture was filtered
  4. washrinsed with DCM
  5. concentrationconcentrated
  6. concentrationThe mixture was concentrated
  7. dissolutionredissolved in 1:1 AcOH
  8. customH2O and purified by preparative HPLC

Sources & evidence

ORD record
ord-c9df6bce06a342de88fd409fc0a198bd
Source dataset
uspto-grants-2011_08
Patent number
US07994209B2

Reaction notes

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