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

HRID 1474696Notes

Reaction equation

HRID 1474696 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].[CH3:14][O:15][CH2:16][C:17]1[CH:18]=[N:19][C:20]([N:23]2[CH2:28][CH2:27][CH:26]([C@H:29]3[CH2:31][C@H:30]3[CH2:32][CH2:33]O)[CH2:25][CH2:24]2)=[N:21][CH:22]=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>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:33][CH2:32][C@@H:30]2[CH2:31][C@@H:29]2[CH:26]2[CH2:27][CH2:28][N:23]([C:20]3[N:19]=[CH:18][C:17]([CH2:16][O:15][CH3:14])=[CH:22][N:21]=3)[CH2:24][CH2:25]2)=[CH:7][C:2]=1[F:1]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 58415153Methyl 2-(2-Fluoro-4-hydroxyphenyl)acetateHCID 895817522-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethanol

Product 1

HCID 89583790Methyl{2-fluoro-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 an RT solution of methyl (2-fluoro-4-hydroxyphenyl)acetate (1.60 g, 5.49 mmol) in 15 ml of anhydrous dichloromethane 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, 4.32 g, 16.5 mmol), and di-tert-butyl azodicarboxylate (2.53 g, 11.0 mmol). The mixture was stirred at RT for 3 hours, filtered through Celite and concentrated. The residue was purified by column chromatography (50 g silica gel) using a gradient eluent of 0-50% ethyl acetate:hexanes (1000 ml) to afford the title compound. LC/MS (m/z) 458.3 (M+H)+.

Workup

  1. filtrationfiltered through Celite
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (50 g silica gel)

Sources & evidence

ORD record
ord-504541f88bc340dca1edef7d36109d5c
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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