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 1915966Notes

Reaction equation

HRID 1915966 reaction equation
[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]

Participants

8

Reactant 6

HCID 6342Acetonitrile2×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

Product 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 esterYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-1e5b7029df2143cbafc9af5b9ce07fbf
Source dataset
uspto-grants-2013_12
Patent number
US08614193B2

Reaction notes

Loading…