Triethylamine → [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-[(E)-4-[9-[2-(tert-butoxycarbonylamino)acetyl]-4,9-diazaspiro[5.5]undecan-4-yl]but-1-enyl]phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate

HRID 2284538Notes

Reaction equation

HRID 2284538 reaction equation
C(N(CC)CC)C.Cl.Cl.[C:10]([O:13][CH2:14][C@@H:15]1[C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@@H:18]([O:29][C:30](=[O:32])[CH3:31])[C@H:17]([N:33]2[C:41]3[C:36](=[C:37]([CH3:42])[CH:38]=[CH:39][CH:40]=3)[C:35]([CH2:43][C:44]3[CH:49]=[CH:48][C:47](/[CH:50]=[CH:51]/[CH2:52][CH2:53][N:54]4[CH2:59][C:58]5([CH2:64][CH2:63][NH:62][CH2:61][CH2:60]5)[CH2:57][CH2:56][CH2:55]4)=[CH:46][CH:45]=3)=[CH:34]2)[O:16]1)(=[O:12])[CH3:11].C1N=CN(C(N2C=NC=C2)=O)C=1.[C:77]([O:81][C:82]([NH:84][CH2:85][C:86](O)=[O:87])=[O:83])([CH3:80])([CH3:79])[CH3:78]>ClCCl>[C:10]([O:13][CH2:14][C@@H:15]1[C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@H:19]([O:25][C:26](=[O:28])[CH3:27])[C@@H:18]([O:29][C:30](=[O:32])[CH3:31])[C@H:17]([N:33]2[C:41]3[C:36](=[C:37]([CH3:42])[CH:38]=[CH:39][CH:40]=3)[C:35]([CH2:43][C:44]3[CH:49]=[CH:48][C:47](/[CH:50]=[CH:51]/[CH2:52][CH2:53][N:54]4[CH2:59][C:58]5([CH2:60][CH2:61][N:62]([C:86](=[O:87])[CH2:85][NH:84][C:82]([O:81][C:77]([CH3:79])([CH3:78])[CH3:80])=[O:83])[CH2:63][CH2:64]5)[CH2:57][CH2:56][CH2:55]4)=[CH:46][CH:45]=3)=[CH:34]2)[O:16]1)(=[O:12])[CH3:11]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 118021334[(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-[(E)-4-(4,9-diazaspiro[5.5]undecan-4-yl)but-1-enyl]phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate dihydrochloride

Product 1

HCID 118021722[(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-[(E)-4-[9-[2-(tert-butoxycarbonylamino)acetyl]-4,9-diazaspiro[5.5]undecan-4-yl]but-1-enyl]phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetateYield 450%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add 4N HCl in 1,4-dioxane (112 5 mmol) to a solution of tert-butyl 4-[(E)-4-[4-[[4-methyl-1-[(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-(acetoxymethyl)tetrahydropyran-2-yl]indol-3-yl]methyl]phenyl]but-3-enyl]-4,9-diazaspiro[5.5]undecane-9-carboxylate (22.5 mmol) in dichloromethane (200 mL) at room temperature. Stir for 3 hours, then concentrate under reduced pressure to yield crude [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-[(E)-4-(4,9-diazaspiro[5.5]undecan-4-yl)but-1-enyl]phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate dihydrochloride (22.5 mmol): MS (m/z): 758.0 (M+H). Add triethylamine (112 5 mmol) to a solution of [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[[4-[(E)-4-(4,9-diazaspiro[5.5]undecan-4-yl)but-1-enyl]phenyl]methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate dihydrochloride (22 5 mmol) in dichloromethane (200 mL). In a separate flask, add CDI (28.1 mmol) portion wise to a solution of 2-(tert-butoxycarbonylamino)acetic acid (27 mmol) in dichloromethane (50 mL). After stirring for 45 minutes at room temperature, add the solution to the previously prepared amine solution and stir at room temperature for 1 hour. Wash with a concentrated sodium bicarbonate solution (200 mL) and brine (200 ml). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure to yield crude title compound (21.6 g, 22.5 mmol): MS (m/z): 915.2 (M+H).

Workup

  1. stirringstir at room temperature for 1 hour
  2. washWash with a concentrated sodium bicarbonate solution (200 mL) and brine (200 ml)
  3. dry with materialDry the organics over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-b4fc23ce2de44a8197d163e36c982f51
Source dataset
uspto-grants-2015_09
Patent number
US09145435B2

Reaction notes

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