Lithium hydroxide, monohydrate → HCID 71186413, compound

HRID 712921Notes

Reaction equation

HRID 712921 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:30]=[CH:29][C:6]([CH2:7][N:8]2[CH2:13][CH:12]3[CH:10]([CH2:11]3)[CH:9]2[C:14]([NH:16][C@H:17]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=2)[CH3:18])=[O:15])=[CH:5][CH:4]=1.O[Li].O>O1CCOCC1.O>[F:31][C:2]([F:1])([F:32])[C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:13][CH:12]3[CH:10]([CH2:11]3)[CH:9]2[C:14]([NH:16][C@H:17]([C:19]2[CH:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[CH:27][CH:28]=2)[CH3:18])=[O:15])=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71186314HCID 71186314, compound

Product 1

HCID 71186413HCID 71186413, compoundYield 36.5%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

To a mixture of methyl 4-((1S)-1-(3-(4-(trifluoromethyl)benzyl)-3-azabicyclo[3.1.0]hexane-2-carboxamido)ethyl)benzoate (D153) (84 mg, 0.19 mmol) in a 1:1 mixture dioxane/water, LiOH H2O (12 mg, 0.28 mmol) was added and the reaction heated at 150° C. under microwave irradiation for 5 min. Dioxane was evaporated off and the aqueous phase was acidified with CH3CO2H. The precipitate (58 mg) was filtered off and submitted for chiral HPLC separation (Preparative chromatographic conditions: Column: DAICEL AD-H; Mobile phase: n-heptane/EtOH/TFA 60%/40%/0.2% v/v; DAD: 235 nm). Solvent evaporation of second eluted peak from chiral column, afforded the title compound (E37) (30 mg)

Workup

  1. additionwas added
  2. customDioxane was evaporated off
  3. filtrationThe precipitate (58 mg) was filtered off
  4. customsubmitted for chiral HPLC separation (Preparative chromatographic conditions
  5. customSolvent evaporation of second eluted peak from chiral column

Sources & evidence

ORD record
ord-b2da6d4b71f747c78bde309d932abc54
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

Loading…