Aluminium lithium hydride → (S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate

HRID 473104Notes

Reaction equation

HRID 473104 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:21](OC)=[O:22])[CH:18]=2)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:22][CH2:21][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[CH2:13][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:20]2

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 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-ylcarbamateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To (S)-methyl 2-(benzyloxycarbonylamino)-2,3-dihydro-1H-indene-5-carboxylate (7.38 mmol, 2.4 g) at 0° C. in THF (36.9 mL) under an argon atmosphere was added Lithium aluminium hydride in THF (7.38 mmol, 7.38 mL) dropwise. The reaction was left to stir for 1.5 hrs at 0 degrees. The reaction was quenched with water before the addition of 5N HCl (aq) to adjust the pH to 3. DCM was added before separating the aqueous and washing once with water and once with brine. The DCM layer was dried over MgSO4 before removing the solvent in vacuo. The crude product was purified by silica chromatography (2:1 Heptane/EtOAc to 2:1 EtOAc/Heptane, 100 g silica cartridge) to give the product as a white solid (1.8 g, 82%). 1H NMR (400 MHz, CDCl3) δ 1.60 (t, 1H), 2.81 (m, 2H), 3.27 (m, 2H), 4.53 (d, 1H), 4.66 (d, 2H), 4.95 (brs, 1H), 5.12 (s, 2H), 7.17 (d, 2H), 7.23 (m, 1H), 7.33 (m, 5H).

Workup

  1. waitThe reaction was left
  2. customThe reaction was quenched with water before the addition of 5N HCl (aq)
  3. additionDCM was added
  4. custombefore separating the aqueous and
  5. washwashing once with water and once with brine
  6. dry with materialThe DCM layer was dried over MgSO4
  7. custombefore removing the solvent in vacuo
  8. customThe crude product was purified by silica chromatography (2:1 Heptane/EtOAc to 2:1 EtOAc/Heptane, 100 g silica cartridge)

Sources & evidence

ORD record
ord-3aad87eb262c450f9240905618a42c4a
Source dataset
uspto-grants-2014_01
Patent number
US08633237B2

Reaction notes

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