Triphenylphosphine → HCID 89583930, compound

HRID 1474740Notes

Reaction equation

HRID 1474740 reaction equation
[N:1]1([C:5](=[O:16])[CH2:6][C:7]2[C:12]([F:13])=[CH:11][C:10]([OH:14])=[CH:9][C:8]=2[F:15])[CH2:4][CH2:3][CH2:2]1.[CH2:17]([C:19]1[CH:20]=[N:21][C:22]([N:25]2[CH2:30][CH2:29][CH:28]([C@H:31]3[CH2:33][C@H:32]3[CH2:34][CH2:35]O)[CH2:27][CH2:26]2)=[N:23][CH:24]=1)[CH3:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[N:1]1([C:5](=[O:16])[CH2:6][C:7]2[C:8]([F:15])=[CH:9][C:10]([O:14][CH2:35][CH2:34][C@@H:32]3[CH2:33][C@@H:31]3[CH:28]3[CH2:27][CH2:26][N:25]([C:22]4[N:21]=[CH:20][C:19]([CH2:17][CH3:18])=[CH:24][N:23]=4)[CH2:30][CH2:29]3)=[CH:11][C:12]=2[F:13])[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 895828981-(Azetidin-1-yl)-2-(2,6-difluoro-4-hydroxyphenyl)ethanoneHCID 1176784962-((1S,2R)-2-(1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol

Product 1

HCID 89583930HCID 89583930, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(azetidin-1-yl)-2-(2,6-difluoro-4-hydroxyphenyl)ethanone (50.0 mg, 0.128 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of 2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (38.0 mg, 0.182 mmol), triphenylphosphine (polymer-bound, 143 mg, 0.412 mmol), and di-tert-butyl azodicarboxylate (84.0 mg, 0.363 mmol). The reaction mixture was stirred at RT for 3 hours. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-100% acetonitrile in 0.1% formic acid in water gradient), to give the title compound. LC/MS (m/z) 485.3 (M+H)+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationconcentrated under reduced pressure
  3. filtrationThe residue was filtered
  4. custompurified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-100% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-6c35e04c2c4643aabff7191ad7266568
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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