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

HRID 1474661Notes

Reaction equation

HRID 1474661 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[Cl:13][C:14]1[CH:15]=[N:16][C:17]([N:20]2[CH2:25][CH2:24][CH:23]([C@H:26]3[CH2:28][C@H:27]3[CH2:29][CH2:30]O)[CH2:22][CH2:21]2)=[N:18][CH:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Cl:13][C:14]1[CH:15]=[N:16][C:17]([N:20]2[CH2:25][CH2:24][CH:23]([C@H:26]3[CH2:28][C@H:27]3[CH2:29][CH2:30][O:1][C:2]3[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:7]=3)[CH2:22][CH2:21]2)=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 518900Benzeneacetic acid, 4-hydroxy-, methyl esterHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol

Product 1

HCID 89583877Methyl [4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of methyl (4-hydroxyphenyl)acetate (106 mg, 0.639 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of 2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (150 mg, 0.532 mmol) in 5 ml anhydrous dichloromethane, triphenylphosphine (polymer-bound, 419 mg, 1.21 mmol), and di-test-butyl azodicarboxylate (245 mg, 1.07 mmol). The reaction mixture was stirred at RT for 3 hours. It was filtered by Celite® and concentrated. The residue was purified by column chromatography on silica gel (50 g) using a gradient eluent of 0-50% ethyl acetate in hexanes (1000 ml) to afford the title compound. LC/MS (m/z) 430.3 (M+H)+.

Workup

  1. filtrationIt was filtered by Celite®
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography on silica gel (50 g)

Sources & evidence

ORD record
ord-a88294d4eba442bbbf66f4f895443d38
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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