2-Dimethylaminopyridine → 17-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone

HRID 1991025Notes

Reaction equation

HRID 1991025 reaction equation
[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([OH:51])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([O:56][Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])[CH2:6][C:5]1=[O:64])[CH:2]=[CH2:3].[C:65]([Si:69]([CH3:83])([CH3:82])[O:70][C:71](=[O:81])[CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][C:78](O)=[O:79])([CH3:68])([CH3:67])[CH3:66].CN(C1C=CC=CN=1)C.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.O.C(Cl)Cl>[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][C:78](=[O:79])[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73][CH2:72][C:71]([O:70][Si:69]([C:65]([CH3:67])([CH3:66])[CH3:68])([CH3:82])[CH3:83])=[O:81])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([O:56][Si:57]([C:60]([CH3:61])([CH3:62])[CH3:63])([CH3:58])[CH3:59])[CH2:6][C:5]1=[O:64])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 218852-DimethylaminopyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23080810O-mono(tert-butyl-dimethyl-silanyl)octanedioic acidHCID 7379247117-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone

Product 1

HCID 8660279117-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraoneYield 24.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Procedure

A mixture of 17-allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone (138 mg, 0.15 mmol), O-mono(tert-butyl-dimethyl-silanyl)octanedioic acid (86.7 mg, 0.218 mmol), dimethylaminopyridine (DMAP; 16.5 mg, 0.098 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC/HCl; 69.1 mg, 0.261 mmol) and methylene chloride (CH2Cl2; 1 ml) was stirred at room temperature for 1.5 hours. The reaction product was poured over an ethyl acetate-water mixed solution and extracted. The organic phase obtained was washed with water and saline, and dried over magnesium sulfate (MgSO4). After the MgSO4 was separated by filtration, the filtrate was concentrated under reduced pressure. The residue thus obtained was purified using a silica gel column (eluted with 20% AcOEt (in n-hexane)) to yield the desired 17-allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone (44 mg, 24.6%).

Workup

  1. extractionextracted
  2. customThe organic phase obtained
  3. washwas washed with water and saline
  4. dry with materialdried over magnesium sulfate (MgSO4)
  5. customAfter the MgSO4 was separated by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified
  9. washa silica gel column (eluted with 20% AcOEt (in n-hexane))

Sources & evidence

ORD record
ord-74b771e702054713861d20565a774e25
Source dataset
uspto-grants-2010_01
Patent number
US07645614B2

Reaction notes

Loading…