Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → HCID 57546118, compound

HRID 913919Notes

Reaction equation

HRID 913919 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:21][OH:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:32]=[C:31]([C:33](=[N+]=[N-])[C:34]([O:36][CH3:37])=[O:35])[C:30]2[C:26](=[CH:27][N:28]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[N:29]=2)[CH:25]=1>C1C=CC=CC=1.C(OCC)(=O)C.CCCCCC.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.[Rh+2].[Rh+2]>[Cl:23][C:24]1[CH:32]=[C:31]([CH:33]([O:22][CH2:21][C:8]2([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:12][CH2:13]2)[C:34]([O:36][CH3:37])=[O:35])[C:30]2[C:26](=[CH:27][N:28]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:46])([CH3:45])[CH3:47])[N:29]=2)[CH:25]=1

Participants

6

Reactant 2

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 76561042Methyl 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-diazoacetate

Product 1

HCID 57546118HCID 57546118, compound

Reagents, catalysts & solvents 3

HCID 152122Dirhodium tetraacetateCatalystHCID 241BenzeneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent2×

Procedure

To a suspension of tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (2.26 g, 7.30 mmol) and rhodium(II) acetate dimer (4.84 mg, 11 μmol) in benzene (4 mL) at reflux was added a solution of methyl 2-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-diazoacetate (1.39 g, 3.65 mmol) in benzene (3 mL) via syringe pump over 60 h. After addition was complete, the reaction was cooled. It became a very viscous solution. The reaction mixture was diluted with 20% ethyl acetate/n-hexane and loaded onto a column. Column chromatography (20% ethyl acetate/n-hexane→25% ethyl acetate/n-hexane) gave 1.88 g (78%) as a yellow foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.03 (s, 1H), 7.58 (d, J=1.8 Hz, 1H), 7.29 (dd, J=8.5, 5.2 Hz, 2H), 7.06 (s, 1H), 6.97 (dd, J=8.9, 8.5 Hz, 2H), 5.68 (d, J=10.7 Hz, 1H), 5.65 (d, J=10.7 Hz, 1H), 5.42 (s, 1H), 3.71 (bs, 2H), 3.61 (s, 3H), 3.60 (t, J=8.6 Hz, 2H), 3.39 (d, J=8.9 Hz, 1H), 3.03 (m, 2H), 2.16 (m, 1H), 2.08 (m, 1H), 1.93 (m, 2H), 1.42 (s, 9H), 0.91 (t, J=8.2 Hz, 2H), −0.05 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 170.5, 161.5 (d, J=246 Hz), 155.0, 145.6, 138.3, 128.9 (d, J=7.7 Hz), 127.9, 125.5, 122.8, 122.5, 119.5, 115.2 (d, J=21 Hz), 82.1, 79.4, 78.6, 76.4, 67.7, 52.3, 41.4, 40.0 (br), 32.1, 31.9, 28.6, 17.9, −1.4. Mass spec.: 662.53 (MH)+.

Workup

  1. temperatureat reflux
  2. additionAfter addition
  3. temperaturethe reaction was cooled

Sources & evidence

ORD record
ord-f7d29eebdc3b4e8fb109879a6a6a53d4
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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