Hydrochloric Acid → {(2S,4R)-1-[(1S)-4-Methyl-1-(3-methylbutyl)pent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid

HRID 1942293ノート

反応式

HRID 1942293 の反応式
[Li+].[OH-].[CH3:3][C:4](=[CH2:34])[C:5]#[C:6][C@@H:7]([N:13]1[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]([O:22]C)=[O:21])[CH2:15][C@H:14]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:8][CH2:9][CH:10]([CH3:12])[CH3:11].Cl>O.C1COCC1>[CH3:34][C:4](=[CH2:3])[C:5]#[C:6][C@@H:7]([N:13]1[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]([OH:22])=[O:21])[CH2:15][C@H:14]1[C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:28][CH:29]=1)[CH2:8][CH2:9][CH:10]([CH3:12])[CH3:11]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59201188Methyl {(2S,4R)-1-[(1S)-4-methyl-1-(3-methylbutyl)pent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

生成物 1

HCID 24860889{(2S,4R)-1-[(1S)-4-Methyl-1-(3-methylbutyl)pent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid収率 93.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of LiOH (67 mg, 2.8 mmol) in H2O (1 ml) was added to a stirred solution of methyl {(2S,4R)-1-[(1S)-4-methyl-1-(3-methylbutyl)pent-4-en-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Step 1, 250 mg, 0.56 mmol) in THF (2 ml) at RT. The mixture was stirred at RT for 18 hrs, then at 60° C. for 3 hrs. After cooling to RT 2N HCl was added and the THF was removed in vacuo. The residue was partitioned between CH2Cl2/H2O. The pH of the aqueous layer was adjusted to ˜pH7 with saturated aqueous NaHCO3. The aqueous layer was extracted with CH2Cl2 (×3). The combined extracts were dried (Na2SO4) filtered and evaporated. The residue was purified by chromatography (silica, 4% MeOH/CH2Cl2) to give the acid (228 mg) as a colourless foam. 1H NMR (500 MHz, CD3OD): δ 0.83 (6H, d, J 6.6), 1.12-1.20 (2H, m), 1.33-1.43 (3H, m), 1.58 (2H, q, J 7.8), 1.80 (1H, dd, J 2.8, 12.8), 1.85-1.91 (5H, s), 2.18-2.26 (2H, m), 2.48 (1H, t, J 11.1), 2.98-3.04 (1H, m), 3.16 (1H, t, J 7.6), 3.55 (1H, dd, J 2.5, 11.3), 5.21 (1H, s), 5.24 (1H, s), 7.53 (2H, d, J 7.6), 7.62 (2H, d, J 8.2); M/Z (ES+) 436 (MH+).

後処理

  1. waitat 60° C. for 3 hrs
  2. additionwas added
  3. customthe THF was removed in vacuo
  4. customThe residue was partitioned between CH2Cl2/H2O
  5. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography (silica, 4% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-b043aa92c239426eb57703fc9208f0a0
出典データセット
uspto-grants-2013_03
特許番号
US08389547B2

反応ノート

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