Acetic Acid → (2R)-2-[({6-[4-fluoro-3-(trifluoromethyl)phenyl]pyridin-2-yl}methyl)amino]-3-methylbutan-1-ol

HRID 1472924ノート

反応式

HRID 1472924 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH:14]=O)[CH:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17].[NH2:20][C@@H:21]([CH2:25][OH:26])[CH:22]([CH3:24])[CH3:23].C(O)(=O)C.C([BH3-])#N>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([CH2:14][NH:20][C@H:21]([CH:22]([CH3:24])[CH3:23])[CH2:25][OH:26])[CH:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[C:16]([F:19])([F:18])[F:17]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 6950587D-ValinolHCID 848199696-(4-Fluoro-3-(trifluoromethyl)phenyl)picolinaldehyde

生成物 1

HCID 68312365(2R)-2-[({6-[4-fluoro-3-(trifluoromethyl)phenyl]pyridin-2-yl}methyl)amino]-3-methylbutan-1-ol収率 59%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of Example 267A (0.500 g, 1.86 mmol) in methanol (20 mL) at ambient temperature was added D-valinol (0.20 mL, 1.9 mmol) and acetic acid (0.40 mL, 7.4 mmol) followed by MP-cyanoborohydride (2.49 mmol/g; 1.0 g). After 2 hours, the mixture was filtered, concentrated and the residue partitioned between ether and 1M NaOH. The organic extract was concentrated and purified by chromatography to provide 390 mg (59%) of the title compound. MS (DCI+) m/z 270 (M+H); 1H NMR (500 MHz, CDCl3) δ 8.28 (dd, J=6.8, 2.0 Hz, 1H), 8.24-8.15 (m, 1H), 7.76 (t, J=7.7 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.34-7.25 (m, 2H), 4.04 (q, J=14.5 Hz, 2H), 3.70 (dd, J=10.9, 4.0 Hz, 1H), 3.49 (dd, J=10.8, 6.9 Hz, 1H), 2.53 (td, J=6.7, 4.1 Hz, 1H), 1.97-1.85 (m, 1H), 1.04 (d, J=6.8 Hz, 3H), 0.97 (d, J=6.9 Hz, 3H).

後処理

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. customthe residue partitioned between ether and 1M NaOH
  4. extractionThe organic extract
  5. concentrationwas concentrated
  6. custompurified by chromatography

出典と根拠

ORDレコード
ord-d364635489bd4bcd967dadf304a741d0
出典データセット
uspto-grants-2015_04
特許番号
US09012651B2

反応ノート

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