Dichloromethane → 2,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane

HRID 574618ノート

反応式

HRID 574618 の反応式
[CH3:1][C:2]1[S:3][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[CH2:5][N:6]=1.Cl.CO.C([BH3-])#N.[Na+].ClCCl>CO.CC1C(Br)=C(O)C(Br)=CC=1C1(C2C=C(Br)C(O)=C(Br)C=2C)OS(=O)(=O)C2C=CC=CC1=2>[CH3:1][CH:2]1[NH:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[S:3]1

参加物

7

反応物 4

HCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 101764151-Methylpiperidine-4-spiro-(2'-methylthiazoline)HCID 21893726Hydrochloride methanol2 回

生成物 1

HCID 669939622,8-Dimethyl-1-thia-3,8-diazaspiro[4.5]decane収率 19.5%

試薬・触媒・溶媒 2

HCID 6451Bromocresol Green触媒HCID 887Methanol溶媒

実験手順

To a stirred solution of 2,8-dimethyl-1-thia-3,8-diaza-spiro[4.5]dec-2-ene (10.4 ml, 60 mmol) in methanol (150 ml) at room temperature, bromocresol green (5 mg) was added and the solution became blue. 4N HCl/MeOH was added to the stirred solution until the color changed to yellow. Sodium cyanoborohydride (3.9 gr, 62 mmol) was then added in one portion and the resulting mixture was stirred at room temperature for 2 h. During this period, each time that the reaction color changed to green, more 4N HCl/MeOH was added to keep the solution color yellow. At the end of this time, the solvent was evaporated under reduced pressure to give blue-green oil. Dichloromethane (100 ml) was added to the residue and the mixture was washed with 2N NaOH (50 ml). The two phases were separated and the aqueous phase was extracted with dichloromethane (100 ml). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography (silica, CH2Cl2/MeOH/NH4OH 90/10/1) to give the title compound (2.18 g) as an almost colorless oil. 1H NMR (CDCl3, 500 MHz) δ 4.61 (q, J=6.18 Hz, 1H, CHCH3), 3.10 (d, J=12.6 Hz, 1H, CHHNH), 2.74 (d, J=12.6 Hz, 1H, CHHNH), 2.27-2.19 (m, 1H), 2.23 (s, 3H, NCH3), 2.10 (m, 2H), 1.85-1.70 (m, 5H), 1.46 (d, J=6.18 Hz, 3H, CH3CH) ppm.

後処理

  1. waitDuring this period
  2. additionwas added
  3. customAt the end of this time, the solvent was evaporated under reduced pressure
  4. customto give blue-green oil
  5. washthe mixture was washed with 2N NaOH (50 ml)
  6. customThe two phases were separated
  7. extractionthe aqueous phase was extracted with dichloromethane (100 ml)
  8. dry with materialdried with anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by flash chromatography (silica, CH2Cl2/MeOH/NH4OH 90/10/1)

出典と根拠

ORDレコード
ord-1b46b0e2d67e49b2bea69bf94c24c6e0
出典データセット
uspto-grants-2015_05
特許番号
US09034891B2

反応ノート

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