Triethylamine → Isotretinoin

HRID 1955363ノート

反応式

HRID 1955363 の反応式
O[CH:2]1[O:6][C:5](=[O:7])[CH:4]=[C:3]1[CH3:8].C(N(CC)CC)C.[CH3:16][C:17]([CH:39]=[CH:40][C:41]1[C:46]([CH3:48])([CH3:47])[CH2:45][CH2:44][CH2:43][C:42]=1[CH3:49])=[CH:18][CH2:19][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[Mg+2].[Cl-]>CCCCCCC.CN(C)C(=O)C>[CH3:49][C:42]1[CH2:43][CH2:44][CH2:45][C:46]([CH3:47])([CH3:48])[C:41]=1/[CH:40]=[CH:39]/[C:17](/[CH3:16])=[CH:18]/[CH:19]=[CH:2]/[C:3](/[CH3:8])=[CH:4]\[C:5]([OH:6])=[O:7]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 1153012(5H)-Furanone, 5-hydroxy-4-methyl-HCID 164726[3-Methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienyl] triphenyl phosphoniumHCID 5360315Magnesium Chloride

生成物 1

HCID 5282379Isotretinoin

試薬・触媒・溶媒 2

HCID 8900Heptane溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
15 °C

実験手順

N,N-dimethylacetamide (300 milliliters (mL)) , 5-hydroxy-4-methyl-2[5H]-furanone (26.81 grams (g)), 235 millimoles (mmol), 1.2 equivalents), and triethylamine (164 mL,1.2 moles, 6 equivalents) were added to 107.26 g (197 mmol) of [3-methyl-5-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4-pentadienyl] triphenyl phosphonium salt. The resulting mixture was cooled to 15° C. prior to addition of magnesium chloride (30.03 g, 315 mmol, 1.6 equivalents). The reaction mixture was allowed to stir at room temperature for 17 hours. The reaction solution was washed with 200 mL of heptane. Toluene (100 mL) was added and the solution was acidified with 280 mL of 20% by volume HCl . The aqueous layer was back-extracted three times, each time with 200 mL of a 9:1 heptane:toluene mixture. The combined organic layers were washed with aqueous methanol, water, and then concentrated to give an orange solid. Heptane (250 mL) was added to the crude solid and the slurry was cooled to 0° C. and then filtered. Acetone (200 mL) and heptane (800 mL) were added to the solid and the resulting mixture was stirred at 25° C. Filtration of this slurry provided isotretinoin with >98% purity as a solid. 1H NMR: (300 MHz, CDCl3):δ 1.03(s,6; H), 1.44-1.68(m,4H), 1.72(s,3H), 1.88-2.05(m,2H), 2.0(s,3H), 2.11 (d,3H), 5.67(s,1H), 6.15-6.32(m,3H), 7.03 (dd,1H), 7.76 (d,1H).

後処理

  1. washThe reaction solution was washed with 200 mL of heptane
  2. additionToluene (100 mL) was added
  3. extractionThe aqueous layer was back-extracted three times
  4. washThe combined organic layers were washed with aqueous methanol, water
  5. concentrationconcentrated
  6. customto give an orange solid
  7. temperaturethe slurry was cooled to 0° C.
  8. filtrationfiltered
  9. additionAcetone (200 mL) and heptane (800 mL) were added to the solid
  10. stirringthe resulting mixture was stirred at 25° C
  11. filtrationFiltration of this slurry

出典と根拠

ORDレコード
ord-4f710e3958934aada8e95763a5a48533
出典データセット
uspto-grants-2000_09
特許番号
US06124485

反応ノート

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