3-Phenoxybenzaldehyde → HCID 68769797、化合物

HRID 1173012

反応式

HRID 1173012 の反応式
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([O:17][C:18]([C@@H:20]1[CH2:22][C@H:21]1[C:23]1[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][CH:24]=1)=[O:19])[CH3:16].[O:30]([C:37]1[CH:38]=[C:39]([CH:42]=[CH:43][CH:44]=1)[CH:40]=O)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClC(Cl)C>[CH2:15]([O:17][C:18]([C@@H:20]1[CH2:22][C@H:21]1[C:23]1[CH:24]=[CH:25][C:26]([NH:29][CH2:40][C:39]2[CH:42]=[CH:43][CH:44]=[C:37]([O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:38]=2)=[CH:27][CH:28]=1)=[O:19])[CH3:16]

参加物

5

反応物 3

HCID 382843-PhenoxybenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 68767952rac-ethyl (1R,2R)-2-(4-aminophenyl)cyclopropane-1-carboxylate

生成物 1

HCID 68769797HCID 68769797、化合物収率 77%

試薬・触媒・溶媒 1

HCID 63651,1-Dichloroethane溶媒

実験手順

Sodium triacetoxyborohydride (0.30 g, 1.40 mmol) was added to a solution of (−)-(trans)-ethyl-2-(4-aminophenyl)cyclopropanecarboxylate (III-1a) (0.116 g, 0.56 mmol) and 3-phenoxybenzaldehyde (1.15 g, 0.56 mmol) in 5 mL of dichloroethane. The mixture was stirred at room temperature for one hour and then partitioned between chloroform and saturated aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate and the solvent evaporated. The residue was purified by chromatography (silica gel, hexane:ethyl acetate) to give (−)-(trans)-ethyl-2-[4-({[3-(phenyloxy)phenyl]methyl}amino)phenyl]cyclopropanecarboxylate (III-2a) (0.167 g, 77%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.34-7.26 (m, 3H), 7.11 (t, J=7.32 Hz, 2H), 7.02 (m, 1H), 6.99 (d, J=8.60 Hz, 2H), 6.92 (d, J=8.42 Hz, 2H), 6.89 (m, 1H), 6.54 (d, J=8.60 Hz, 2H), 4.19 (s, 2H), 4.17 (q, J=7.14 Hz, 2H), 4.03 (br s, 1H), 2.44 (m, 1H), 1.78 (m, 1H), 1.52 (m, 1H), 1.28 (t, J=7.14 Hz, 3H), 1.25 (m, 1H). ES-MS m/z 388 (MH+). Aqueous sodium hydroxide (1.0 mL of a 25% solution) was added to a solution of III-2a (0.167 g, 0.43 mmol) in 4 mL of methanol and the mixture was heated at reflux for 8 hours. The volatile solvents were removed under vacuum, water was added, and the pH was adjusted to 5 with saturated aqueous sodium bisulfate. The mixture was extracted with dichloromethane, the organic phase was dried over sodium sulfate and concentrated to give 0.192 g of the title compound (III-3a) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.34 (t, J=8.42 Hz, 2H), 7.29 (t, J=7.87 Hz, 1H), 7.10 (m, 2H), 6.98 (s, 1H), 6.93 (d, J=7.68 Hz, 2H), 6.81 (d, J=8.42 Hz, 1H), 6.75 (d, J=8.23 Hz, 2H), 6.42 (d, J=8.42 Hz, 2H), 6.08 (m, 1H), 4.20 (m, 2H), 2.02 (m, 1H), 1.44 (m, 1H), 1.15 (m, 1H), 0.91 (m, 1H). ES-MS m/z 360 (MH+). [α]25,D=−187° (dichloromethane, c=4). Product was determined to be >99% ee by chiral SFC according to Method 1.

後処理

  1. custompartitioned between chloroform and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. customthe solvent evaporated
  4. customThe residue was purified by chromatography (silica gel, hexane:ethyl acetate)

出典と根拠

ORDレコード
ord-bf9926d98d37431a8116defba89b754d
出典データセット
uspto-grants-2010_11
特許番号
US07834013B2

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