Di-tert-butyl azodicarboxylate → methyl (2-fluoro-4-{2-[(1S,2R)-2-{1-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)acetate

HRID 1850782Notes

Reaction equation

HRID 1850782 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][OH:20])[CH2:11][CH2:10]2)[O:6][N:5]=1.[F:21][C:22]1[CH:27]=[C:26](O)[CH:25]=[CH:24][C:23]=1[CH2:29][C:30]([O:32][CH3:33])=[O:31].N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:21][C:22]1[CH:27]=[C:26]([O:20][CH2:19][CH2:18][C@@H:16]2[CH2:17][C@@H:15]2[CH:12]2[CH2:11][CH2:10][N:9]([C:7]3[O:6][N:5]=[C:4]([CH2:3][O:2][CH3:1])[N:8]=3)[CH2:14][CH2:13]2)[CH:25]=[CH:24][C:23]=1[CH2:29][C:30]([O:32][CH3:33])=[O:31]

Participants

6

Reactant 3

HCID 97268Di-tert-butyl azodicarboxylateHCID 58415153Methyl 2-(2-Fluoro-4-hydroxyphenyl)acetate2×HCID 867111842-((1S,2R)-2-{1-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}cyclopropyl)ethanol

Product 1

HCID 70856014methyl (2-fluoro-4-{2-[(1S,2R)-2-{1-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}cyclopropyl]ethoxy}phenyl)acetate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 11776TriphenylphosphineSolvent

Procedure

To a solution of 2-[(1S,2R)-2-{1-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}cyclopropyl]ethanol (0.900 g, 3.20 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of methyl (2-fluoro-4-hydroxyphenyl)acetate (Intermediate 1, 0.707 g, 3.84 mmol) in 10 ml anhydrous dichloromethane, triphenylphosphine, polymer-bound (2.52 g, 12.6 mmol), and di-tert-butyl azodicarboxylate (1.47 g, 6.40 mmol). The reaction mixture was stirred at RT for 3 hours. It was filtered by Celite and concentrated. The residue was purified on Biotage column (100 g silica gel) using a gradient eluent of 0-50% ethyl acetate in hexanes (700 ml) to afford the title compound. LC/MS (m/z) 448.2 (M+H)+.

Workup

  1. filtrationIt was filtered by Celite
  2. concentrationconcentrated
  3. customThe residue was purified on Biotage column (100 g silica gel)

Sources & evidence

ORD record
ord-c1cb73fb77d3451aaf3b475407baf6d9
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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