Hydrochloric Acid → N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]-L-phenylalanine

HRID 74825Notes

Reaction equation

HRID 74825 reaction equation
C1C2C(COC([NH:18][C@H:19]([C:23]([N:25]([CH3:62])[C@@H:26]([C@@H:58]([CH3:61])[CH2:59][CH3:60])[C@H:27]([O:56][CH3:57])[CH2:28][C:29]([N:31]3[CH2:35][CH2:34][CH2:33][C@H:32]3[C@H:36]([O:54][CH3:55])[C@@H:37]([CH3:53])[C:38]([NH:40][C@H:41]([C:49]([O:51]C)=[O:50])[CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:39])=[O:30])=[O:24])[CH:20]([CH3:22])[CH3:21])=O)C3C(=CC=CC=3)C=2C=CC=1.[OH-].[Li+].O.Cl>C1COCC1>[CH3:55][O:54][C@@H:36]([C@@H:32]1[CH2:33][CH2:34][CH2:35][N:31]1[C:29](=[O:30])[CH2:28][C@@H:27]([O:56][CH3:57])[C@@H:26]([N:25]([CH3:62])[C:23](=[O:24])[C@H:19]([CH:20]([CH3:21])[CH3:22])[NH2:18])[C@@H:58]([CH3:61])[CH2:59][CH3:60])[C@@H:37]([CH3:53])[C:38]([NH:40][C@H:41]([C:49]([OH:51])=[O:50])[CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 86685782methyl N-{(2R,3R)-3-[(2S)-1-{(3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoyl}pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninate

Product 1

HCID 86685781N-{(2R,3R)-3-methoxy-3-[(2S)-1-{(3R,4S,5S)-3-methoxy-5-methyl-4-[methyl(L-valyl)amino]heptanoyl]pyrrolidin-2-yl]-2-methylpropanoyl]-L-phenylalanineYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of #113 (2.10 g, 2.46 mM) in 10 mL of THF, lithium hydroxide (228 mg, 5.16 mM) was added followed by 3 mL of water. The reaction was allowed to stir at room temperature for 2 hours. The reaction was acidified though the addition of 1 M HCl and then concentrated in vacuo. The resulting white solid was taken up in 20 mL of acetonitrile and mL of water. The aqueous layer removed and the organic layer was washed once with water. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Ethyl acetate (20 mL) was then added and the crude solid was allowed to stir for 30 minutes, before being filtered to yield a white solid #250 (1.42 g, 94%). LC-MS (Protocol Q): m/z 619.5 [M+H+], retention time=1.10 minutes. HPLC (Protocol A at 45° C.) m/z 619.4 [M+H+], retention time=6.732 minutes.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe aqueous layer removed
  3. washthe organic layer was washed once with water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. additionEthyl acetate (20 mL) was then added
  8. stirringto stir for 30 minutes
  9. filtrationbefore being filtered

Sources & evidence

ORD record
ord-18784d524b5042bd8df69b45cb47ace5
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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