Hydrochloric Acid → HCID 67705253, compound

HRID 2172999Notes

Reaction equation

HRID 2172999 reaction equation
[OH-].[Li+].C([O:6][CH2:7][C:8]([NH:10][C@H:11]1[C@@H:16]2[C@@H:14]([C@H:15]2[C:17]([O:19]CC)=[O:18])[C@:13]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])([C:22]([O:24]CC)=[O:23])[C@@H:12]1[O:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=1)=[O:9])(=O)C.Cl>O1CCCC1>[C:31]([O:30][C:28]([NH:27][C@@:13]1([C:22]([OH:24])=[O:23])[C@H:12]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[C:39]([Cl:44])[CH:38]=2)[C@@H:11]([NH:10][C:8](=[O:9])[CH2:7][OH:6])[C@@H:16]2[C@H:14]1[C@H:15]2[C:17]([OH:19])=[O:18])=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3939Lithium Hydroxide2×HCID 86695981HCID 86695981, compound

Product 1

HCID 67705253HCID 67705253, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Add 1M aqueous lithium hydroxide (4.0 mL, 4.0 mmol) to a solution of diethyl (1S,2R,3R,4S,5R,6S)-4-[(2-acetoxyacetyl)amino]-2-(tert-butoxycarbonylamino)-3-[(3,4-dichlorophenyl)methoxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.42 g, 0.67 mmol) in tetrahydrofuran (7.0 mL) at room temperature and stir overnight. Acidify the reaction to approximately pH 1 with 5N aqueous HCl. Extract with ethyl acetate (3×25 mL). Dry the combined organic layers, filter, and conc. under reduced pressure. HPLC analysis of crude reaction mixture shows starting material present. Add a 1M aqueous lithium hydroxide (4.0 mL, 4.0 mmol) to a solution of the crude reaction mixture in tetrahydrofuran (7.0 mL) and heat at 50° C. After 17 hours, acidify reaction to approximately pH 1 with 5N aqueous HCl. Extract with ethyl acetate (3×25 mL). Dry the combined extracts, filter, and conc. under reduced pressure. Purify by preparative reverse-phase high performance liquid chromatography using a gradient of 95% water (with 0.03% HCl)/5% acetonitrile to 5% water (with 0.03% HCl)/95% acetonitrile over 40 min. to provide (1S,2R,3R,4S,5R,6S)-2-(tert-butoxycarbonylamino)-3-[(3,4-dichlorophenyl)methoxy]-4-[(2-hydroxyacetyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid (0.181 g, 0.34 mmol, 51%) as a white solid. MS (m/z): 531 (M−H).

Workup

  1. extractionExtract with ethyl acetate (3×25 mL)
  2. customDry the combined organic layers
  3. filtrationfilter
  4. customHPLC analysis of crude reaction mixture
  5. waitAfter 17 hours
  6. extractionExtract with ethyl acetate (3×25 mL)
  7. customDry the combined extracts
  8. filtrationfilter
  9. customPurify by preparative reverse-phase high performance liquid chromatography
  10. customover 40 min.

Sources & evidence

ORD record
ord-dca7d4bd6db140bb9a01743df5d8471b
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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