Triphenylphosphine → Methyl{2,6-difluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}acetate

HRID 1474725Notes

Reaction equation

HRID 1474725 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([F:9])[C:3]=1[CH2:10][C:11]([O:13][CH3:14])=[O:12].[CH3:15][O:16][CH2:17][C:18]1[CH:19]=[N:20][C:21]([N:24]2[CH2:29][CH2:28][CH:27]([C@H:30]3[CH2:32][C@H:31]3[CH2:33][CH2:34]O)[CH2:26][CH2:25]2)=[N:22][CH:23]=1.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>[CH3:14][O:13][C:11](=[O:12])[CH2:10][C:3]1[C:2]([F:1])=[CH:7][C:6]([O:8][CH2:34][CH2:33][C@@H:31]2[CH2:32][C@@H:30]2[CH:27]2[CH2:28][CH2:29][N:24]([C:21]3[N:20]=[CH:19][C:18]([CH2:17][O:16][CH3:15])=[CH:23][N:22]=3)[CH2:25][CH2:26]2)=[CH:5][C:4]=1[F:9]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 68228239Benzeneacetic acid, 2,6-difluoro-4-hydroxy-, methyl esterHCID 895817522-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethanol

Product 1

HCID 117684495Methyl{2,6-difluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of methyl (2,6-difluoro-4-hydroxyphenyl)acetate (1.46 g, 7.22 mmol) in 10 ml anhydrous dichloromethane at RT was added a solution of 2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethanol (2.10 g, 7.22 mmol) in 20 ml anhydrous dichloromethane, followed by triphenylphosphine (polymer-bound, 3.79 g, 11.4 mmol), and di-tert-butyl azodicarboxylate (1.83 g, 7.94 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 purified by column chromatography on silica gel (Biotage column, 50 g) using a gradient eluent of 0-40% ethyl acetate in hexanes (900 ml) to afford the title compound. LC/MS (m/z) 476.4 (M+H)+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by column chromatography on silica gel (Biotage column, 50 g)

Sources & evidence

ORD record
ord-ef5f619f1acf4a1cb5b85813b9c4f7ae
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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