Benzyl mercaptan → 3-(3-(Benzylthio)phenyl)-1-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclobutanol

HRID 2280859Notes

Reaction equation

HRID 2280859 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[CH2:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]4[C:22]([C:29]5[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=5[Cl:36])=[N:23][O:24][C:25]=4[CH:26]4[CH2:28][CH2:27]4)=[CH:15][C:14]=3[Cl:37])([OH:12])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[C:44]1([CH2:50][SH:51])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.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]>[CH2:50]([S:51][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]4[C:22]([C:29]5[C:34]([Cl:35])=[CH:33][CH:32]=[CH:31][C:30]=5[Cl:36])=[N:23][O:24][C:25]=4[CH:26]4[CH2:28][CH2:27]4)=[CH:15][C:14]=3[Cl:37])([OH:12])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 712054233-(3-Bromophenyl)-1-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclobutanol

Product 1

HCID 712054163-(3-(Benzylthio)phenyl)-1-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclobutanolYield 30.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of compound 2b (619 mg, 1 mmol) in toluene (20 mL) under argon atmosphere were added K2CO3 (276 mg, 2 mmol), phenylmethanethiol (125 mg, 1 mmol), Pd2(dba)3 (200 mg, 0.22 mmol) and Xantphos (75 mg, 0.16 mmol). Then the mixture was stirred at 115° C. for 4 h. After being cooled to rt, the reaction was diluted with water (100 mL) and extracted with EA (100 mL×2). The combined organic layers were washed with brine (100 mL×2), dried over Na2SO4 and concentrated to dryness. Purification by CC gave compound the compound 5a (200 mg; 30%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ: 7.36-7.32 (m, 3H), 7.28-7.07 (m, 9H), 7.01 (d, J=7.2 Hz, 1H), 6.82 (d, J=2.0 Hz, 1H), 6.66 (dd, J=8.8, 2.0 Hz, 1H), 4.75 (s, 2H), 4.04 (s, 2H), 3.06-3.00 (m, 2H), 2.84-2.78 (m, 2H), 2.44-2.38 (m, 3H), 2.09 (m, 1H), 1.24-1.18 (m, 2H), 1.11-1.08 (m, 2H). MS (ESI+) m/z: 662 [M+1]+.

Workup

  1. temperatureAfter being cooled to rt
  2. extractionextracted with EA (100 mL×2)
  3. washThe combined organic layers were washed with brine (100 mL×2)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. customPurification by CC

Sources & evidence

ORD record
ord-d360dd8dea0c4b4d9daae8c27c805097
Source dataset
uspto-grants-2015_09
Patent number
US09139539B2

Reaction notes

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