Aluminium lithium hydride → Benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-1-ylcarbamate

HRID 43019Notes

Reaction equation

HRID 43019 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]1[C:20]2[C:15](=[CH:16][C:17]([CH2:21][N:22]3[CH:26]=[C:25]([C:27](OCC)=[O:28])[C:24]([C:32]([F:35])([F:34])[F:33])=[N:23]3)=[CH:18][CH:19]=2)[CH2:14][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:28][CH2:27][C:25]1[C:24]([C:32]([F:34])([F:35])[F:33])=[N:23][N:22]([CH2:21][C:17]2[CH:16]=[C:15]3[C:20](=[CH:19][CH:18]=2)[CH:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:14]3)[CH:26]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 67088120Ethyl 1-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 67088172Benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-1-ylcarbamateYield 74.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 1-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (5.21 mmol, 2.54 g) in THF (40 mL) at 0° C. was added lithium aluminium hydride (5.21 mmol, 5.21 mL) in a dropwise fashion. The whole was stirred at room temperature for 2 h before the reaction mixture was quenched by the dropwise addition of methanol followed by sat Rochelle's salt. The organics were extracted with DCM (2×100 mL) and dried (1PS paper) before being concentrated under reduced pressure. The residue was purified by flash chromatography (100 g, 1:1 EtOAc/heptane) to give a white solid (1.72 g, 3.86 mmol, 74.1%). 1H NMR (400 MHz, CDCl3) δ 1.85 (m, 2H) 2.60 (m, 1H) 2.85 (m, 1H) 2.95 (m, 1H) 4.63 (brs, 2H) 5.00 (d, 1H) 5.14 (s, 2H) 5.20 (m, 1H) 5.25 (s, 2H) 7.09 (d, 2H) 7.34 (m, 7H).

Workup

  1. customwas quenched by the dropwise addition of methanol
  2. extractionThe organics were extracted with DCM (2×100 mL)
  3. customdried (1PS paper)
  4. concentrationbefore being concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography (100 g, 1:1 EtOAc/heptane)

Sources & evidence

ORD record
ord-3dc70a585325441b96fb3e67ff7918e2
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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