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Lithium Hydroxide → 1-((3aS,8aR)-8,8a-Dihydro-2,2-dimethyl-2H-indeno(1,2-d)oxazol-3(3aH)-yl)-3-phenyl-1-propanone

HRID 1018723
Notes
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Reaction equation

HRID 1018723 reaction equation
[OH-].[Li+].[NH2:3][C@@H:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][C@@H:5]1[OH:13].[F-].[K+].CO[C:18]([CH3:20])=[CH2:19].C(Cl)CCC1C=CC=CC=1.[C:31](Cl)(=[O:40])[CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[CH2-]C(C)=O>C1COCC1>[CH3:20][C:18]1([CH3:19])[N:3]([C:31](=[O:40])[CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@H:4]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[CH2:6][C@H:5]2[O:13]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 7

HCID 3939Lithium Hydroxide2×HCID 7706(3-Chloropropyl)benzeneHCID 83002-MethoxypropeneHCID 64801Benzenepropanoyl chlorideHCID 522689Potassium FluorideHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 178477758
HCID 178477758, compound

Product 1

HCID 98835981-((3aS,8aR)-8,8a-Dihydro-2,2-dimethyl-2H-indeno(1,2-d)oxazol-3(3aH)-yl)-3-phenyl-1-propanoneYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Solid lithium hydroxide (anhydrous) (21.55 g, 0.9 mole, 0.9 equiv.) was added to a 3-neck Morton flask equipped with a mechanical stirrer, condenser, thermocouple and nitrogen. Solid (−)-cis-aminoindan-2-ol (3, 149.19 g, 1.0 mole) was then added, followed by dry THF (1.492 L, to give ˜100 g/l batch) at 20° C. The resulting slurry was stirred at 350 RPM. The KF of the solution was <1200 mg/l. 2-Methoxypropene (383.1 ml, 288.47 g, 4.0 mole, 4.0 equiv.) was then added subsurfacely. The flask was then placed in a 20° C. water bath, and neat hydrocinnamoyl chloride (2, 153.02 ml, 173.68 g, 1.03 mole, 1.03 equiv.) was added over 1.25 hours. At about 50% hydrocinnamoyl chloride addition, the solution became clear. At about 90% addition an exotherm occured (5-10° C.). Upon completion of the addition of 2 the batch was warmed to 40° C. and aged until >99.0% conversion (as measured by HPLC assay) to acetonide 1 was achieved. Additional lithium hydroxide (5.99 g, 0.25 mole, 0.25 eq.) was added to the batch to quench excess HCl by-product. The batch was stirred for one hour. Upon quench the batch turned from clear to golden in appearance. Residual HCl was determined by titration to be less than 0.005 mmol. The solution yield was 98%.

Workup

  1. customequipped with a mechanical stirrer, condenser
  2. customwas then placed in a 20° C.
  3. additionAt about 90% addition an exotherm
  4. custom(5-10° C.)
  5. additionUpon completion of the addition of 2 the batch
  6. customto quench excess HCl by-product
  7. stirringThe batch was stirred for one hour
  8. customUpon quench the batch

Sources & evidence

ORD record
ord-2c12d3aa0a56443e829c9dbe7948dad0
Source dataset
uspto-grants-2002_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06482952B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes