Hydrochloric Acid → (2R,4R,5R)-4-(4-Methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1,2-dicarboxylic acid 1-benzyl ester

HRID 2246973Notes

Reaction equation

HRID 2246973 reaction equation
CC[O:3][C:4]([C@H:6]1[CH2:11][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C@@H:9]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]3[O:30][CH2:29][CH2:28][N:27]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:26]=3[CH:36]=2)[CH2:8][N:7]1[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])=[O:5].[OH-].[Li+].Cl.CCOC(C)=O.CCCCCCC.C(O)(=O)C>CO.O1CCCC1.O>[CH2:40]([O:39][C:37]([N:7]1[CH2:8][C@H:9]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]3[O:30][CH2:29][CH2:28][N:27]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:26]=3[CH:36]=2)[C@@H:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:11][C@@H:6]1[C:4]([OH:5])=[O:3])=[O:38])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 68443015(2R,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1,2-dicarboxylic acid 1-benzyl ester 2-ethyl esterHCID 86619247EtOAc heptane acetic acid

Product 1

HCID 68439824(2R,4R,5R)-4-(4-Methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1,2-dicarboxylic acid 1-benzyl ester

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

A solution of 0.370 g (2R,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1,2-dicarboxylic acid 1-benzyl ester 2-ethyl ester in 18 ml methanol-tetrahydrofuran-water 1:1:1 is cooled to 0° C. Lithiumhydroxide (0.050 g) is added and the mixture is left to warm to room temperature and stirred for 16 hours at this temperature. The mixture is acidified with 1M hydrochloric acid and extracted with dichloro-methane (2×). The combined organic phases are dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified via flash chromatography (SiO2 60 F) to provide the product as a light red wax. Rf=0.25 (EtOAc-heptane-acetic acid 20:10:1); Rt=4.95.

Workup

  1. waitthe mixture is left
  2. extractionextracted with dichloro-methane (2×)
  3. dry with materialThe combined organic phases are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified via flash chromatography (SiO2 60 F)
  7. customto provide the product as a light red wax

Sources & evidence

ORD record
ord-509d6ccb15c54e17870fda6577885e20
Source dataset
uspto-grants-2010_03
Patent number
US07687495B2

Reaction notes

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