Aluminium lithium hydride → HCID 85471821, compound

HRID 2177370Notes

Reaction equation

HRID 2177370 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH2:17][O:18][C:19]3[C:24]([F:25])=[CH:23][C:22]([CH2:26][CH2:27][C:28](OCC)=[O:29])=[CH:21][C:20]=3[F:33])=[C:10]([C:13]([F:16])([F:15])[F:14])[S:11][CH:12]=2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([CH2:17][O:18][C:19]3[C:20]([F:33])=[CH:21][C:22]([CH2:26][CH2:27][CH2:28][OH:29])=[CH:23][C:24]=3[F:25])=[C:10]([C:13]([F:16])([F:14])[F:15])[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 90418507HCID 90418507, compound

Product 1

HCID 85471821HCID 85471821, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 25-mL 2-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed ethyl 3-(4-[[4-(4-chlorophenyl)-2-(trifluoromethyl)thiophen-3-yl]methoxy]-3,5-difluorophenyl)propanoate (60 mg, 0.12 mmol, 1.00 equiv), tetrahydrofuran (3.0 mL). This was followed by the addition of a solution of LiAlH4 (11.3 mg, 0.30 mmol, 2.51 equiv) in tetrahydrofuran (3.0 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 2 h at 25° C. The reaction progress was monitored by LCMS/TLC (ethyl acetate/petroleum ether=1:6). The reaction was then quenched by the addition of 5 mL of water and 2 mL 2N HCl. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a TLC-Plate with ethyl acetate/petroleum ether (1:1.5). This resulted in 0.041 g (75%) of 3-(4-[[4-(4-chlorophenyl)-2-(trifluoromethyl)thiophen-3-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a white solid. 1H NMR (CD3OD, 300 Hz): 7.70 (s, 1H), 7.49 (d, J=8.6 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 6.80 (d, J=9.3 Hz, 2H), 5.09 (s, 2H), 3.57 (t, J=6.3 Hz, 2H), 2.65 (t, J=7.5 Hz, 2H), 1.76-1.86 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C21H16C1F5O2S, 485.0 (M+Na). found 485.2.

Workup

  1. customInto a 25-mL 2-necked round-bottom flask (1 atm) purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 2 h at 25° C
  4. customThe reaction was then quenched by the addition of 5 mL of water and 2 mL 2N HCl
  5. extractionThe resulting solution was extracted with 3×10 mL of ethyl acetate
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThis resulted in 0.041 g (75%) of 3-(4-[[4-(4-chlorophenyl)-2-(trifluoromethyl)thiophen-3-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a white solid

Sources & evidence

ORD record
ord-456a60fcc9cf470fb32bceb462384df7
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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