Lithium hydroxide, monohydrate → HCID 86709720, compound

HRID 2285424Notes

Reaction equation

HRID 2285424 reaction equation
C[O:2][C:3]([C:5]1([CH3:46])[CH2:10][CH2:9][CH2:8][N:7]([C:11](=[O:45])[C@@H:12]([NH:14][C:15](=[O:44])[C@@H:16]([NH:20][C:21](=[O:43])[C:22]([CH3:42])([CH3:41])/[CH:23]=[CH:24]/[C:25]2[CH:34]=[C:33]3[C:28]([CH:29]=[CH:30][C:31]([C@H:35]([O:37]C(=O)C)[CH3:36])=[N:32]3)=[CH:27][CH:26]=2)[CH:17]([CH3:19])[CH3:18])[CH3:13])[NH:6]1)=[O:4].O.[OH-].[Li+]>O1CCCC1.O>[OH:37][C@@H:35]([C:31]1[CH:30]=[CH:29][C:28]2[C:33](=[CH:34][C:25](/[CH:24]=[CH:23]/[C:22]([CH3:42])([CH3:41])[C:21]([NH:20][C@@H:16]([CH:17]([CH3:19])[CH3:18])[C:15]([NH:14][C@@H:12]([CH3:13])[C:11]([N:7]3[CH2:8][CH2:9][CH2:10][C:5]([CH3:46])([C:3]([OH:4])=[O:2])[NH:6]3)=[O:45])=[O:44])=[O:43])=[CH:26][CH:27]=2)[N:32]=1)[CH3:36]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86709721HCID 86709721, compound

Product 1

HCID 86709720HCID 86709720, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-[(S)-2-((S)-2-{(E)-4-[2-((R)-1-acetoxy-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoylamino}-3-methyl-butyrylamino)-propionyl]-3-methyl-hexahydro-pyridazine-3-carboxylic acid methyl ester (790 mg, 1.24 mmol) in tetrahydrofuran/water (60 mL, 5:1) at 0° C. was added lithium hydroxide monohydrate (380 mg, 9.04 mmol). After stirring at 0° C. for 5 h, the reaction was quenched with hydrochloric acid (1 M, 12 mL). The volatiles were removed in vacuo and residual acetic acid and methanol were azeotroped off with toluene (3×). The residue was partitioned between ethyl acetate and water. After separation of the layers, the aqueous phase was extracted with ethyl acetate (4×) and dichloromethane (5×). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford the title compound (668 mg, 93%) as a pale yellow solid and as a 1:1 mixture of diastereoisomers. LCMS (m/z) 582 [M+H], Tr=1.54 min.

Workup

  1. customthe reaction was quenched with hydrochloric acid (1 M, 12 mL)
  2. customThe volatiles were removed in vacuo and residual acetic acid and methanol
  3. customwere azeotroped off with toluene (3×)
  4. customThe residue was partitioned between ethyl acetate and water
  5. customAfter separation of the layers
  6. extractionthe aqueous phase was extracted with ethyl acetate (4×) and dichloromethane (5×)
  7. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c538878f007141d4a6393753c931e6a3
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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