Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate → 2-(4-((2-(3-Chlorophenyl)-6-cyclopropylpyrimidin-4-yl)methyl)phenyl)ethanol

HRID 1508915Notes

Reaction equation

HRID 1508915 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](OC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:26]3[CH2:28][CH2:27]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][OH:23])=[CH:19][CH:20]=3)[CH:11]=[C:10]([CH:26]3[CH2:27][CH2:28]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 90112009Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate

Product 1

HCID 903384902-(4-((2-(3-Chlorophenyl)-6-cyclopropylpyrimidin-4-yl)methyl)phenyl)ethanolYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

A 25-mL round bottom flask was charged with methyl 2-(4-((2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl)methyl)phenyl)acetate (0.149 g, 0.38 mmol) and THF (5 mL) at Borane-dimethylsulfide complex (0.108 mL, 1.13 mmol) was added and the resulting solution was stirred at 55° C. for 2.5 h until the starting material was consumed (monitored by LCMS analysis). The reaction was quenched with methanol then treated with 2N aqueous HCl (5 drops) and concentrated under reduced pressure. The residue was diluted with methanol and then concentrated under reduced pressure. The residue was absorbed onto silica (2 g) and purified by column chromatography on silica using hexanes/ethyl acetate (10:0 to 3:1) as the eluent to afford the title compound (0.113 g, 82%) as a colorless oil. MW=364.87. 1H NMR (DMSO-d6, 500 MHz) δ 8.31-8.27 (m, 2H), 7.59-7.51 (m, 2H), 7.27 (s, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.16 (d, J=8.0 Hz, 2H), 4.58 (t, J=5.0 Hz, 1H), 4.04 (s, 2H), 3.59-3.52 (m, 2H), 2.68 (t, J=7.0 Hz, 2H), 2.16-2.09 (m, 1H), 1.16-1.05 (m, 4H); APCI MS m/z 365 [M+H]+.

Workup

  1. additionwas added
  2. customwas consumed (monitored by LCMS analysis)
  3. customThe reaction was quenched with methanol
  4. additionthen treated with 2N aqueous HCl (5 drops)
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was diluted with methanol
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was absorbed onto silica (2 g)
  9. custompurified by column chromatography on silica

Sources & evidence

ORD record
ord-9749c3f8c71e4951a4aecd532a153bc0
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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