Hydrochloric Acid → [(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

HRID 2284537Notes

Reaction equation

HRID 2284537 reaction equation
[ClH:1].O1CCOCC1.[CH3:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[C:11]([CH2:41][C:42]1[CH:47]=[CH:46][C:45](/[CH:48]=[CH:49]/[CH2:50][CH2:51][N:52]3[CH2:57][C:56]4([CH2:62][CH2:61][N:60](C(OC(C)(C)C)=O)[CH2:59][CH2:58]4)[CH2:55][CH2:54][CH2:53]3)=[CH:44][CH:43]=1)=[CH:12][N:13]2[C@H:18]1[C@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@@H:22]([O:28][C:29](=[O:31])[CH3:30])[C@H:21]([O:32][C:33](=[O:35])[CH3:34])[C@@H:20]([CH2:36][O:37][C:38](=[O:40])[CH3:39])[O:19]1>ClCCl>[ClH:1].[ClH:1].[C:38]([O:37][CH2:36][C@@H:20]1[C@@H:21]([O:32][C:33](=[O:35])[CH3:34])[C@H:22]([O:28][C:29](=[O:31])[CH3:30])[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:18]([N:13]2[C:14]3[C:10](=[C:9]([CH3:8])[CH:17]=[CH:16][CH:15]=3)[C:11]([CH2:41][C:42]3[CH:47]=[CH:46][C:45](/[CH:48]=[CH:49]/[CH2:50][CH2:51][N:52]4[CH2:57][C:56]5([CH2:58][CH2:59][NH:60][CH2:61][CH2:62]5)[CH2:55][CH2:54][CH2:53]4)=[CH:44][CH:43]=3)=[CH:12]2)[O:19]1)(=[O:40])[CH3:39]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 118021687tert-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

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-c69e68886c424c56be8b0cc20048b4c2
Source dataset
uspto-grants-2015_09
Patent number
US09145435B2

Reaction notes

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