Chloroform → HCID 59371623, compound

HRID 2095349Notes

Reaction equation

HRID 2095349 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C@H:9]([OH:17])[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:5]=[CH:6][CH:7]=1.[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([Sn](C)(C)C)[CH:36]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C(Cl)(Cl)Cl.[F-].[Cs+].P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>CN1CCCC1=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:36]=[C:35]([C:2]2[CH:3]=[C:4]([CH2:8][C@H:9]([OH:17])[CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:5]=[CH:6][CH:7]=2)[CH:34]=[N:33][CH:32]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

8

Reactant 5

HCID 6212ChloroformHCID 25953Cesium fluorideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 105744715-Iodo-A-85380, 5-trimethylstannyl N-boc derivativeHCID 593714201-(3-bromophenyl)-3-phenyl-2(R)-propanol

Product 1

HCID 59371623HCID 59371623, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution/suspension of 1-(3-bromophenyl)-3-phenyl-2(R)-propanol (291 mg, 1.00 mmol), 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (427 mg, 1.00 mmol, 1.00 equiv.), Pd2(dba)3.CHCl3 (15.5 mg, 15 μmol, 15 mequiv.) and CsF (304 mg, 2.00 mmol, 2.00 equiv.) in N-methylpyrrolidone (1.0 mL) contained in a dried 100 mL round-bottom flask was added P(t-Bu)3 (10 wt % in hexane, 106 μL) by syringe at room temperature under N2. The mixture was stirred for 3 h at 80° C., after which time TLC analysis indicated that the starting material had disappeared. After cooling, the reaction was quenched with saturated aqueous NH4Cl solution, and the mixture was extracted with EtOAc (3×50 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated under vacuum. The residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether/aqueous NH3 1:10:0.1-1:1:0.1 to give the product (381 mg, 80%) as a yellowish oil. 1H NMR (CDCl3, 300 MHz) δ 8.47 (s, 1H), 4.34 (s, 1H), 7.47-7.26 (m, 10H), 4.56 (m, 1H), 4.41 (m, 1H), 4.21 (dd, 1H, J=10.0, 3.0 Hz), 4.18-4.11 (m, 2H), 3.93 (t, 2H, J=6.6 Hz), 3.01-2.78 (m, 4H), 2.42-2.20 (m, 2H), 1.42 (s, 9H).

Workup

  1. temperatureAfter cooling
  2. customthe reaction was quenched with saturated aqueous NH4Cl solution
  3. extractionthe mixture was extracted with EtOAc (3×50 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. washwas eluted with EtOAc/petroleum ether/aqueous NH3 1:10:0.1-1:1:0.1

Sources & evidence

ORD record
ord-89eba0e29a9b459bbf2a5247dfafe808
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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