Aluminium lithium hydride → HCID 66747301, compound

HRID 2279393Notes

Reaction equation

HRID 2279393 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C([O:9][C:10]([C@H:12]1[C@@H:17]([NH:18][C:19]([C:21]2[CH:22]=[CH:23][C:24]3[S:29][CH2:28][C:27](=[O:30])[NH:26][C:25]=3[CH:31]=2)=[O:20])[CH2:16][CH2:15][N:14]([CH2:32][CH2:33][O:34][C:35]2[CH:44]=[N:43][C:42]3[C:37](=[CH:38][C:39]([O:45][CH3:46])=[CH:40][CH:41]=3)[N:36]=2)[CH2:13]1)=O)C>O1CCCC1>[OH:9][CH2:10][C@@H:12]1[C@@H:17]([NH:18][C:19]([C:21]2[CH:22]=[CH:23][C:24]3[S:29][CH2:28][C:27](=[O:30])[NH:26][C:25]=3[CH:31]=2)=[O:20])[CH2:16][CH2:15][N:14]([CH2:32][CH2:33][O:34][C:35]2[CH:44]=[N:43][C:42]3[C:37](=[CH:38][C:39]([O:45][CH3:46])=[CH:40][CH:41]=3)[N:36]=2)[CH2:13]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 66746364HCID 66746364, compound

Product 1

HCID 66747301HCID 66747301, compoundYield 14.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

Lithium aluminium hydride (1.0M solution in tetrahydrofuran, 80 μL, 0.08 mmol, 1.0 eq) is added dropwise at −10° C. to a stirred solution of (3R,4S)-1-[2-(7-methoxy-quinoxalin-2-yloxy)-ethyl]-4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidine-3-carboxylic acid ethyl ester (50 mg, 0.08 mmol, 1.0 eq) in tetrahydrofuran (5 mL). After 30 minutes stirring at −10° C., the reaction mixture is cautiously quenched with ice-water (2 mL). Tetrahydrofuran is evaporated and the crude is extracted with dichloromethane (3×10 mL) and water (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by preparative HPLC to afford (3S,4S)-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid {3-hydroxymethyl-1-[2-(7-methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-amide as a yellow lyophilizated powder (6 mg, 14% yield).

Workup

  1. customthe reaction mixture is cautiously quenched with ice-water (2 mL)
  2. customTetrahydrofuran is evaporated
  3. extractionthe crude is extracted with dichloromethane (3×10 mL) and water (10 mL)
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue that
  8. customis purified by preparative HPLC

Sources & evidence

ORD record
ord-bf0e8e04306740349dbec4858fa64551
Source dataset
uspto-grants-2015_09
Patent number
US09133219B2

Reaction notes

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