Dicyclohexylcarbodiimide → benzyl [(S)-p-t-butoxy-alpha-[[4-[(t-butoxycarbonyl)methoxy]-piperidino]carbonyl]phenethyl]carbamate

HRID 1290021ノート

反応式

HRID 1290021 の反応式
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:25]([OH:27])=O)[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(N=C=NC2CCCCC2)CCCCC1.[NH:43]1[CH2:48][CH2:47][CH:46]([O:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:45][CH2:44]1>C(OCC)(=O)C.ON1C(=O)CCC1=O>[C:21]([O:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:25]([N:43]2[CH2:44][CH2:45][CH:46]([O:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][CH2:48]2)=[O:27])=[CH:15][CH:16]=1)([CH3:22])([CH3:23])[CH3:24]

参加物

6

反応物 3

HCID 10868DicyclohexylcarbodiimideHCID 978520O-(1,1-Dimethylethyl)-N-((phenylmethoxy)carbonyl)-L-tyrosineHCID 10036224Tert-butyl (piperidin-4-yloxy)-acetate

生成物 1

HCID 10415568benzyl [(S)-p-t-butoxy-alpha-[[4-[(t-butoxycarbonyl)methoxy]-piperidino]carbonyl]phenethyl]carbamate収率 85%

試薬・触媒・溶媒 2

HCID 80170N-Hydroxysuccinimide触媒HCID 8857Ethyl Acetate溶媒3 回

実験手順

11.14 g (30 mmol) of N-(benzyloxycarbonyl)-O-(1,1-dimethylethyl)-L-tyrosine were dissolved in 65 ml of ethyl acetate while warming to 40°. The solution was treated at 20° with 0.1 g (0.9 mmol) of N-hydroxysuccinimide. Subsequently, a solution of 7.5 g (36 mmol) of dicyclohexylcarbodiimide in 40 ml of ethyl acetate was added dropwise at 22° within 25 minutes. A white suspension formed during the addition and this was stirred for 30 minutes. A solution of 7.8 g (36 mmol) of t-butyl (4-piperidinyloxy)acetate in 100 ml of ethyl acetate was then added dropwise to the suspension within 30 minutes. A suspension formed and this was stirred at 22° for 3 hours. The precipitated dicyclohexylurea was filtered off and the filtrate was washed with 2N hydrochloric acid, water and semi-saturated sodium bicarbonate solution. The organic phase was dried over sodium sulphate and, after removing the drying agent, evaporated. The residue was a viscous oil and weighed 18.5 g. The oil was diluted with a mixture of 10 ml of ethyl acetate and 60 ml of hexane and warmed to 50°. The insoluble solid was filtered off under suction and the filtrate was treated with 20 ml of hexane and seeded with a small amount of crystalline product at 30°. The mixture was cooled to 0° within one hour and stirred at this temperature for 30 minutes. The crystals were then filtered off under suction and washed on the filter with 20 ml of hexane. 14.5 g (85%) of benzyl [(S)-p-t-butoxy-α-[[4-[(t-butoxycarbonyl)methoxy]-piperidino]carbonyl]phenethyl]carbamate were obtained in this manner. Its content was 96% according to HPLC.

後処理

  1. temperaturewhile warming to 40°
  2. customA white suspension formed during the addition
  3. customA suspension formed
  4. stirringthis was stirred at 22° for 3 hours
  5. filtrationThe precipitated dicyclohexylurea was filtered off
  6. washthe filtrate was washed with 2N hydrochloric acid, water and semi-saturated sodium bicarbonate solution
  7. dry with materialThe organic phase was dried over sodium sulphate
  8. customafter removing the drying agent
  9. customevaporated
  10. additionThe oil was diluted with a mixture of 10 ml of ethyl acetate and 60 ml of hexane
  11. temperaturewarmed to 50°
  12. filtrationThe insoluble solid was filtered off under suction
  13. additionthe filtrate was treated with 20 ml of hexane
  14. customseeded with a small amount of crystalline product at 30°
  15. temperatureThe mixture was cooled to 0° within one hour
  16. stirringstirred at this temperature for 30 minutes
  17. filtrationThe crystals were then filtered off under suction
  18. washwashed on the
  19. filtrationfilter with 20 ml of hexane

出典と根拠

ORDレコード
ord-aed7e576adb14d388d684c22f8b104e1
出典データセット
uspto-grants-1998_05
特許番号
US05750649

反応ノート

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