3-Phenoxybenzaldehyde → HCID 68769797, compound

HRID 1173012Notes

Reaction equation

HRID 1173012 reaction equation
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]

Participants

5

Reactant 3

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

Product 1

HCID 68769797HCID 68769797, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-bf9926d98d37431a8116defba89b754d
Source dataset
uspto-grants-2010_11
Patent number
US07834013B2

Reaction notes

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