Tetrahydrofuran → HCID 70151883, compound

HRID 1017263Notes

Reaction equation

HRID 1017263 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@H:14]([S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH2:15][C@@:9]1([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C@@:10](/[CH:26]=[C:27](/[C:29]1[CH:34]=[C:33]([O:35][C:36]([F:39])([F:38])[F:37])[CH:32]=[CH:31][C:30]=1[O:40][CH:41]1[CH2:43][CH2:42]1)\I)([OH:25])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(C(C)C)C(C)C)C.[O:89]1CCC[CH2:90]1>C(OCC)(=O)C.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]>[CH2:1]([N:8]1[C@H:13]2[CH2:12][CH2:11][C@@:10]3([CH:26]=[C:27]([C:29]4[CH:34]=[C:33]([O:35][C:36]([F:38])([F:39])[F:37])[CH:32]=[CH:31][C:30]=4[O:40][CH:41]4[CH2:42][CH2:43]4)[C:90](=[O:89])[O:25]3)[C@:9]1([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[CH2:15][C@H:14]2[S:16]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)(=[O:17])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 821241,4-Bis(diphenylphosphino)butane2×HCID 86586093HCID 86586093, compound

Product 1

HCID 70151883HCID 70151883, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-2-[(Z)-2-(2-cyclopropyloxy-5-trifluoromethoxyphenyl)-2-iodoethenyl]-1-phenyl-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol (Description 9; 690 mg, 0.86 mmol), 1,4-bis(diphenylphosphino)butane (45 mg, 0.1 mmol), Pd2(dba)3 (140 mg, 1.5 mmol), ethyl di-iso-propyl amine (0.75 ml) and tetrahydrofuran (20 ml) was stirred under an atmosphere of carbon monoxide (1 atm) at +50° C. for 24 hours. Additional portion of 1,4-bis(diphenylphosphino)butane (45 mg, 0.1 mmol) and Pd2(dba)3 (140 mg, 1.5 mmol) were added and the mixture was stirred for an additional 24 hours. After cooling to room temperature the mixture was diluted with ethyl acetate and filtered through a pad of Celite™. The filtrate was concentrated and the residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate 0-35%) to give the title compound (350 mg, 58%).

Workup

  1. stirringthe mixture was stirred for an additional 24 hours
  2. filtrationfiltered through a pad of Celite™
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate 0-35%)

Sources & evidence

ORD record
ord-e7bdb60bea664ec591e85680158a2b72
Source dataset
uspto-grants-2002_11
Patent number
US06479486B2

Reaction notes

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