4-(Trifluoromethyl)benzenemethanol → HCID 68884763, compound

HRID 1269513Notes

Reaction equation

HRID 1269513 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.[C:13](N1C=CN=C1)(N1C=CN=C1)=[O:14].[CH3:25][O:26][C:27](=[O:44])[C:28]([CH3:43])([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C@@H:37]2[CH2:42][CH2:41][CH2:40][NH:39][CH2:38]2)[CH:32]=1)[CH3:29]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][O:8][C:13]([N:39]2[CH2:40][CH2:41][CH2:42][C@@H:37]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([O:30][C:28]([C:27]([O:26][CH3:25])=[O:44])([CH3:29])[CH3:43])[CH:32]=3)[CH2:38]2)=[O:14])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 676844-(Trifluoromethyl)benzenemethanolHCID 682631,1'-CarbonyldiimidazoleHCID 68883040HCID 68883040, compound

Product 1

HCID 68884763HCID 68884763, compoundYield 101.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-(Trifluoromethyl)benzyl alcohol (0.88 g, 5.0 mmol) was dissolved in toluene (5 mL) and followed by the addition of 1,1′-carbonyldiimidazole (0.89 g, 5.5 mmol). The resulting mixture was stirred under nitrogen at rt for 1 h. A solution of (3S)-2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid methyl ester (Preparation 2; Method E) (1.39 g, 5.0 mmol) in toluene (8 mL) was then introduced and the reaction mixture was heated at 60° C. for 2 h. After cooling, the reaction solution was diluted with ethyl acetate (30 mL) and washed with 1 M HCl (30 mL) and brine (30 mL). The separated organic layer was dried over sodium sulfate and concentrated to yield 2.43 g (100%) of (3S)-3-[3-(1-methoxycarbonyl-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester as a light yellow oil: 1H NMR (CDCl3) δ 1.58 (s, 8H), 1.77 (br m, 1H), 2.00 (br m, 1H), 2.61 (br, 1H), 2.80 (br, 2H), 3.74 (s, 3H), 4.21 (br s, 2H), 5.19 (s, 2H), 6.63 (dd, 1H), 6.72 (s, 1H), 6.83 (br d, 1H), 7.16 (t, 1H), 7.46 (br s, 2H), 7.60 (d, 2H); MS m/z (relative intensity) 479 (M+, 25), 420 (20), 395 (20), 276 (20), 220 (60), 202 (42), 176 (45), 159 (100).

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for 2 h
  2. temperatureAfter cooling
  3. washwashed with 1 M HCl (30 mL) and brine (30 mL)
  4. dry with materialThe separated organic layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f68ad9dee378465b901e0db64e0ca3b0
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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