Aluminium lithium hydride → HCID 90418882, compound

HRID 2177282Notes

Reaction equation

HRID 2177282 reaction equation
[Cl:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([CH2:16][CH2:17][C:18](OCC)=[O:19])=[CH:11][C:10]=2[F:23])=[C:5]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[S:4][N:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[Cl:1][C:2]1[C:6]([CH2:7][O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([CH2:16][CH2:17][CH2:18][OH:19])=[CH:11][C:10]=2[F:23])=[C:5]([C:24]2[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[S:4][N:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 90417623HCID 90417623, compound

Product 1

HCID 90418882HCID 90418882, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed ethyl 3-(4-[[3-chloro-5-(4-chlorophenyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propanoate (250 mg, 0.53 mmol, 1.00 equiv), tetrahydrofuran (10 mL). This was followed by the addition of a solution of LAH (60 mg, 1.58 mmol, 2.99 equiv) in tetrahydrofuran (2 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 20 min at 25° C. The reaction was then quenched by the addition of sodium sulfate.H2O. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (30/70). The collected fractions were combined and concentrated under vacuum. This resulted in 103 mg (45%) of 3-(4-[[3-chloro-5-(4-chlorophenyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a off-white solid. 1H-NMR (300 MHz, CDCl3) δ: 7.62 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 6.71-6.91 (m, 1H), 5.01 (s, 2H), 3.64 (t, J=7.5 Hz, 2H), 2.61-2.69 (m, 2H), 1.70-1.90 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C19H15C12F2NO2S, 430.0 (M+H). found 430.0

Workup

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 20 min at 25° C
  4. customThe reaction was then quenched by the addition of sodium sulfate
  5. filtrationThe solids were filtered out
  6. concentrationThe resulting mixture was concentrated under vacuum
  7. concentrationconcentrated under vacuum
  8. customThis resulted in 103 mg (45%) of 3-(4-[[3-chloro-5-(4-chlorophenyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a off-white solid

Sources & evidence

ORD record
ord-86a35625054c4b99a90163fb94621a4b
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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