Lithium borohydride → (S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate

HRID 42996Notes

Reaction equation

HRID 42996 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@H:9]([NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:8]2)=O.[BH4-].[Li+]>C1COCC1.CO>[OH:2][CH2:3][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@H:9]([NH:14][C:15](=[O:16])[O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[CH2:8]2

Participants

5

Reactant 2

HCID 4148881Lithium borohydride3×HCID 67025433(S)-methyl 2-(benzyloxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate

Product 1

HCID 70224068(S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

(S)-methyl-2-(benzyloxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (15.37 mmol, 5.00 g) was dissolved in THF (50 mL) and the vessel purged with nitrogen. Lithium Borohydride (2M, 30.7 mmol, 15.37 mL) was added dropwise followed by methanol (30.7 mmol, 0.985 g). The solution was stirred at room temperature for 6 h before additional lithium borohydride (2M, 15.35 mmol, 7.69 mL) was added. Stirring was continued overnight. A further amount of lithium borohydride was added (2M, 15.35 mmol, 7.69 mL) and stirring continued for 1 h. The reaction was quenched with MeOH then water and concentrated to a light brown residue. This was partitioned between EtOAc (150 mL) and 1N HCl (150 mL) and the phases mixed and separated. The aqueous layer was twice extracted with ethylacetate and combined organics dried, filtered and concentrated to give a brown gum which was dissolved in MeOH (100 mL) and stirred with activated carbon. Filtration through a dicalite pad followed by concentration and purification on silica eluting with 0-2% MeOH/DCM gave (S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate as a beige solid (2.2, 48%). 1H NMR (400 MHz, CDCl3) δ 1.66 (t, 1H) 2.81 (m, 2H) 3.28 (m, 2H) 4.52 (bs, 1H) 4.65 (d, 2H) 4.95 (bs, 1H) 5.09 (bs, 2H) 7.15-7.37 (bm, 8H).

Workup

  1. customthe vessel purged with nitrogen
  2. additionwas added
  3. stirringstirring
  4. waitcontinued for 1 h
  5. customThe reaction was quenched with MeOH
  6. concentrationwater and concentrated to a light brown residue
  7. customThis was partitioned between EtOAc (150 mL) and 1N HCl (150 mL)
  8. additionthe phases mixed
  9. customseparated
  10. extractionThe aqueous layer was twice extracted with ethylacetate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a brown gum which
  14. stirringstirred with activated carbon
  15. filtrationFiltration through a dicalite pad
  16. concentrationfollowed by concentration and purification on silica eluting with 0-2% MeOH/DCM

Sources & evidence

ORD record
ord-6641da7a93994d1fafa9530cc3d74473
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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