Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate → HCID 57546117, compound

HRID 913834Notes

Reaction equation

HRID 913834 reaction equation
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[C:11](=[C:12]([Br:24])[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:14]=2)[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[CH:8]=1)[CH3:6].[OH:32][CH2:33][C:34]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1>ClCCl.C1CCCCC1>[Br:24][C:12]1[N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:21])[CH3:23])[N:14]=[C:15]2[C:11]=1[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[CH:8]=[C:7]2[CH:5]([O:32][CH2:33][C:34]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:45])([CH3:46])[CH3:44])=[O:41])[CH2:36][CH2:35]1)[CH3:6]

Participants

4

Reactant 2

HCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 57546209HCID 57546209, compound

Product 1

HCID 57546117HCID 57546117, compound

Reagents, catalysts & solvents 1

HCID 21916607Dichloromethane cyclohexaneSolvent

Conditions

Temperature
0 °C

Procedure

(±)-1-(3-Bromo-5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate (1.29 g, 2.21 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (0.71 g, 2.43 mmol) were combined in a dichloromethane/cyclohexane mixture (1:1, 8 mL) and cooled to 0° C. The reaction was treated with tetrafluoroboric acid-diethyl ether complex (60 μL, 0.44 mmol), stirred at 0° C. for 1 h, quenched by addition of saturated sodium bicarbonate and diluted with diethyl ether and the layers separated. The ethereal was washed with water (2×), 1 M potassium bisulfate (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethyl acetate/hexanes) gave 840 mg (53%) as a yellow film. 1H-NMR (CDCl3, 500 MHz) δ 7.82 (s, 1H), 7.54 (s, 1H), 7.24-7.27 (m, 2H), 7.18-7.22 (m, 3H), 5.51 (s, 2H), 5.07 (q, J=6.4 Hz, 1H), 3.74 (m, 2H), 3.44-3.51 (m, 2H), 3.27 (d, J=9.2 Hz, 1H), 3.24 (d, J=9.2 Hz, 1H), 2.99-3.03 (m, 2H), 2.11-2.16 (m, 2H), 1.82-1.88 (m, 2H), 1.50 (d, J=6.4 Hz, 3H), 1.43 (s, 9H), 0.70-0.83 (m, 2H), 0.08 (s, 9H). Mass spec.: 736.03 (MNa)+.

Workup

  1. additionThe reaction was treated with tetrafluoroboric acid-diethyl ether complex (60 μL, 0.44 mmol)
  2. customquenched by addition of saturated sodium bicarbonate
  3. additiondiluted with diethyl ether
  4. customthe layers separated
  5. washThe ethereal was washed with water (2×), 1 M potassium bisulfate (2×), brine (2×)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography on silica gel (10% ethyl acetate/hexanes) gave 840 mg (53%) as a yellow film

Sources & evidence

ORD record
ord-1ccb38d0215949909e317ea606b52bad
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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