(R)-N-(8-fluorochroman-4-yl)-2-methoxyacetamide → (R)-8-fluorochroman-4-amine

HRID 605842ノート

反応式

HRID 605842 の反応式
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][C@H:7]2[NH:12]C(=O)COC>Cl.CCO>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][C@H:7]2[NH2:12]

参加物

4

反応物 1

HCID 59799572(R)-N-(8-fluorochroman-4-yl)-2-methoxyacetamide

生成物 1

HCID 46911919(R)-8-fluorochroman-4-amine収率 88.1%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 702Ethanol溶媒

実験手順

A mixture of 8-fluorochroman-4-amine (3.40 g), methyl 2-methoxyacetate (2.44 g) and Novozyme 435 (Aldrich, 0.68 g) in anhydrous tert-butyl methyl ether (75 mL) was heated at reflux under argon for 2 hours (at which time the ratio of acylated to unacylated product was 1:1 by HPLC). The solid that formed upon cooling was collected via filtration and dissolved in EtOAc. The mixture was filtered to remove the biocatalyst and washed once with 0.5M HCl to remove any lingering (S)-amine. The solvent was evaporated and the product was recrystallized from tert-butyl methyl ether to yield (R)—N-(8-fluorochroman-4-yl)-2-methoxyacetamide (0.78 g). The reaction solvent and recrystallization mother liquor was washed 3 times with 0.5 M HCl and concentrated to yield additional (R)—N-(8-fluorochroman-4-yl)-2-methoxyacetamide (0.83 g). The combined acidic aqueous layers were made basic by NaOH and extracted with DCM to yield (S)-8-fluorochroman-4-amine (1.6 g). A solution of (R)—N-(8-fluorochroman-4-yl)-2-methoxyacetamide (0.78 g) in 8M HCl in EtOH (50 mL) was heated at reflux for 4 hours. The solvents were removed from the cooled reaction mixture, the resulting solid was taken up in 50 mL of 0.5M NaOH, salted out with NaCl(s), and extracted 4 times with DCM to yield (R)-8-fluorochroman-4-amine (0.48 g, 87%). The % ee was checked via chiral HPLC: Chiralcel OD-H (0.46×25 cm analytical column, Daicel Chemical Industries) method: isocratic 5% (0.05% TFA/EtOH) 95% (0.05% TFA/Hex), Rt=7.2 min (S)-enantiomer, Rt=9.2 min (R)-enantiomer.

後処理

  1. temperatureat reflux for 4 hours
  2. customThe solvents were removed from the cooled reaction mixture
  3. extractionextracted 4 times with DCM

出典と根拠

ORDレコード
ord-fa59b2c3802f424a90b43c79cd04d541
出典データセット
uspto-grants-2011_03
特許番号
US07915268B2

反応ノート

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