Tetrahydrofuran → Benzyl 2-(Hydroxymethyl)-1-Indolinecarboxylate

HRID 1168499Notes

Reaction equation

HRID 1168499 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[CH2:10][OH:11].C1COCC1.C(=O)(O)[O-].[Na+].[CH2:22]([O:29][C:30](Cl)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O>[OH:11][CH2:10][CH:2]1[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]1[C:30]([O:29][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:31]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 27946642,3-dihydro-1H-indol-2-ylmethanol

Product 1

HCID 2776402Benzyl 2-(Hydroxymethyl)-1-IndolinecarboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution containing 2,3-dihydro-1H-indol-2-ylmethanol (Preparation 5, 4.31 g) and THF (60 mL) is added to a flask containing sodium bicarbonate (24.27 g) and water (15 mL). Benzylchloroformate (4.5 mL) is slowly added. Once addition is complete, the mixture is stirred overnight. The crude mixture is filtered and washed with a large amount of CH2Cl2. The filtrate is poured into water and the separated organic phase is washed with 5% HCl and brine. The organic layer is dried (Na2SO4), filtering, and concentrated to give a yellow oil. The crude product is chromatographed eluting with EtOAc/heptane (1/1) to give 8.11 g (99%) of the title compound as a pale colored oil. Physical characteristics: MS (ESI+) m/z 284 (M+H)+.

Workup

  1. additionis added to a flask
  2. additionOnce addition
  3. filtrationThe crude mixture is filtered
  4. washwashed with a large amount of CH2Cl2
  5. additionThe filtrate is poured into water
  6. washthe separated organic phase is washed with 5% HCl and brine
  7. dry with materialThe organic layer is dried (Na2SO4)
  8. filtrationfiltering
  9. concentrationconcentrated
  10. customto give a yellow oil
  11. customThe crude product is chromatographed
  12. washeluting with EtOAc/heptane (1/1)

Sources & evidence

ORD record
ord-80570e0bd0a348efb18ebb498324194e
Source dataset
uspto-grants-2003_09
Patent number
US06624159B2

Reaction notes

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