Aluminium lithium hydride → HCID 85472360, compound

HRID 2177244Notes

Reaction equation

HRID 2177244 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[C:20]([F:21])=[CH:19][C:18]([CH2:22][CH2:23][C:24](OCC)=[O:25])=[CH:17][C:16]=3[F:29])=[C:11]([C:30]([F:33])([F:32])[F:31])[S:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[C:20]([F:21])=[CH:19][C:18]([CH2:22][CH2:23][CH2:24][OH:25])=[CH:17][C:16]=3[F:29])=[C:11]([C:30]([F:32])([F:33])[F:31])[S:10][N:9]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 117604672HCID 117604672, compound

Product 1

HCID 85472360HCID 85472360, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 25-mL round-bottom flask, was placed ethyl 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propanoate (100 mg, 0.20 mmol, 1.00 equiv), tetrahydrofuran (2 mL). This was followed by the addition of a solution of LAH (7.5 mg, 0.20 mmol, 1.00 equiv) in tetrahydrofuran (1 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 60 min at 0° C. in a water/ice bath. The reaction progress was monitored by TLC/LCMS (ethyl acetate/petroleum ether=1:5). The reaction was then quenched by the addition of 5 mL of water. The resulting solution was extracted with 5×5 mL of ethyl acetate and the organic layers combined. The solvent was removed under vacuum. The crude product (90 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1): Column, C18 silica gel; mobile phase, 0.05% TFA/ACN=4/1 increasing to 0.05% TFA/ACN=0/1 within 20 min; Detector, UV 254 nm. This resulted in 28.9 mg (32%) of 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a off-white solid. 1H NMR (300 MHz, CD3OD) δ 7.79 (d, J=6.6 Hz, 2H), 7.51 (d, J=8.7 Hz, 2H), 6.83 (d, J=9.6 Hz, 2H), 5.19 (s, 2H), 3.56 (t, J=6.3 Hz, 2H), 2.65 (t, J=7.5 Hz, 2H), 1.80-1.85 (m, 2H). Mass spectrum (ESI, m/z): Calcd. for C20H15ClF5NO2S, 464.0 (M+H). found 464.0.

Workup

  1. customInto a 25-mL round-bottom flask, was placed
  2. stirringThe resulting solution was stirred for 60 min at 0° C. in a water/ice bath
  3. customThe reaction was then quenched by the addition of 5 mL of water
  4. extractionThe resulting solution was extracted with 5×5 mL of ethyl acetate
  5. customThe solvent was removed under vacuum
  6. customThe crude product (90 mg) was purified by Flash-Prep-HPLC with the following conditions (IntelFlash-1)
  7. customThis resulted in 28.9 mg (32%) of 3-(4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propan-1-ol as a off-white solid

Sources & evidence

ORD record
ord-4ec33cd9a5c945d2b02994617fe52902
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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