Acetonitrile → (R)-4-((E)-(S)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester

HRID 1915966ノート

反応式

HRID 1915966 の反応式
[C:1]([O:5][C:6](=[O:67])[CH2:7][CH2:8][C@@H:9]([NH:49][C:50](OCC1C2C=CC=CC=2C2C1=CC=CC=2)=[O:51])[C:10](=[O:48])[NH:11][C@@H:12]([C:34](=[O:47])[NH:35][C:36]([C:39](=[O:46])[NH:40][CH2:41][C:42]([O:44][CH3:45])=[O:43])([CH3:38])[CH3:37])[CH2:13][S:14][C:15]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)C1C=CC=CC=1)([CH3:4])([CH3:3])[CH3:2].C(N[CH2:71][CH3:72])C.[OH:73][C@H:74](/[CH:79]=[CH:80]/[CH2:81][CH2:82][S:83][C:84]([C:97]1[CH:102]=[CH:101][CH:100]=[CH:99][CH:98]=1)(C1C=CC=CC=1)[C:85]1[CH:90]=[CH:89][CH:88]=[CH:87][CH:86]=1)[CH2:75]C(O)=O.C1CN([P+](ON2N=N[C:122]3[CH:123]=[CH:124][CH:125]=[CH:126][C:121]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N([CH:142]([CH3:144])[CH3:143])CC)(C)C.[CH3:145]C#N>C(Cl)Cl>[C:1]([O:5][C:6](=[O:67])[CH2:7][CH2:8][C@@H:9]([NH:49][C:50](=[O:51])[CH2:75][C@H:74]([OH:73])/[CH:79]=[CH:80]/[CH2:81][CH2:82][S:83][C:84]([C:72]1[CH:71]=[CH:143][CH:142]=[CH:144][CH:145]=1)([C:97]1[CH:98]=[CH:99][CH:100]=[CH:101][CH:102]=1)[C:85]1[CH:86]=[CH:87][CH:88]=[CH:89][CH:90]=1)[C:10](=[O:48])[NH:11][C@@H:12]([C:34](=[O:47])[NH:35][C:36]([C:39](=[O:46])[NH:40][CH2:41][C:42]([O:44][CH3:45])=[O:43])([CH3:37])[CH3:38])[CH2:13][S:14][C:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:121]1[CH:126]=[CH:125][CH:124]=[CH:123][CH:122]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 6

HCID 6342Acetonitrile2 回HCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 11711429(S,E)-3-Hydroxy-7-(tritylthio)hept-4-enoic acidHCID 86653396(R)-4-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester

生成物 1

HCID 86653395(R)-4-((E)-(S)-3-Hydroxy-7-tritylsulfanyl-hept-4-enoylamino)-4-{(S)-1-[1-(methoxycarbonylmethyl-carbamoyl)-1-methyl-ethylcarbamoyl]-2-tritylsulfanyl-ethylcarbamoyl}-butyric acid tert-butyl ester収率 85%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 5 (1.60 g, 1.73 mmol, 1 eq) in MeCN (35 mL) was added at rt diethylamine (3.5 mL, 10% v/v) dropwise. One hour later, the solution was concentrated in vacuo and co-evaporated with MeCN (2×10 mL), then with CH2Cl2/hexane (5 mL). The resultant oil was then dried under high vacuum for 3 h. To a solution of (E)-(S)-3-hydroxy-7-tritylsulfanyl-hept-4-enoic acid (758 mg, 1.81 mmol, 1.05 eq) and PyBOP (988 mg, 1.90 mmol, 1.1 eq) in MeCN (25 mL) was added at 0° C. diisopropylethylamine (0.75 mL, 4.3 mmol, 2.5 eq) dropwise. After 5 min, the crude amine solution in CH2Cl2 (25 mL) was added dropwise to the reaction mixture. The solution was then warmed to rt overnight. The solvent was removed in vacuo. Purification by column chromatography on silica (eluting with hexane/EtOAc, 1:4) yielded 6 (1.61 g, 1.46 mmol, 85%) as a white solid.

後処理

  1. concentrationOne hour later, the solution was concentrated in vacuo and co-evaporated with MeCN (2×10 mL)
  2. customThe resultant oil was then dried under high vacuum for 3 h
  3. customThe solvent was removed in vacuo
  4. customPurification by column chromatography on silica (eluting with hexane/EtOAc, 1:4)

出典と根拠

ORDレコード
ord-1e5b7029df2143cbafc9af5b9ce07fbf
出典データセット
uspto-grants-2013_12
特許番号
US08614193B2

反応ノート

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