Triethylamine → tert-Butyl 3-(hydroxymethyl)benzylcarbamate

HRID 2112430Notes

Reaction equation

HRID 2112430 reaction equation
ClC(OCC)=O.[C:7]([O:11][C:12]([NH:14][CH2:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=1)[C:19](O)=[O:20])=[O:13])([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C.[BH4-].[Li+].S([O-])(O)(=O)=O.[Na+].C(=O)([O-])O.[Na+]>O1CCCC1.O>[C:7]([O:11][C:12](=[O:13])[NH:14][CH2:15][C:16]1[CH:24]=[CH:23][CH:22]=[C:18]([CH2:19][OH:20])[CH:17]=1)([CH3:10])([CH3:8])[CH3:9]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 516919Sodium BisulfateHCID 27559293-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 4148881Lithium borohydride

Product 1

HCID 2794814tert-Butyl 3-(hydroxymethyl)benzylcarbamateYield 78.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

At 0° C., ethyl chloroformate (1.93 ml, 20 mmol) was added to a solution of 3-(tert-butoxycarbonylaminomethyl)benzoic acid (5.0 g, 20 mmol) and triethylamine (3.33 ml, 24 mmol) in tetrahydrofuran (30 ml). The reaction mixture was stirred for 40 min at 0° C., and the formed precipitation was filtered off. The filtrate was cooled to 0° C. A 2.0 M solution of lithium borohydride in THF (25 ml, 50 mmol) was added. The reaction mixture was stirred for 16 h, while warming up to room temperature. Water was added carefully, until no gas was formed. A 10% solution of sodium hydrogensulphate (10 ml) was added. A saturated solution of sodium hydrogen carbonate (200 ml) was added. The mixture was extracted with ethyl acetate (200 and 100 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/heptane 1:1 as eluent, to give 3.73 g of (3-hydroxymethylbenzyl)carbamic acid tert butylester.

Workup

  1. customthe formed precipitation
  2. filtrationwas filtered off
  3. temperatureThe filtrate was cooled to 0° C
  4. stirringThe reaction mixture was stirred for 16 h
  5. temperaturewhile warming up to room temperature
  6. customwas formed
  7. extractionThe mixture was extracted with ethyl acetate (200 and 100 ml)
  8. dry with materialThe combined organic layers were dried over magnesium sulphate
  9. customThe solvent was removed in vacuo
  10. customThe crude product was purified by flash chromatography on silica (80 g)

Sources & evidence

ORD record
ord-bc42696fc7e84b8f8dbd67c635e66ec7
Source dataset
uspto-grants-2009_04
Patent number
US07524813B2

Reaction notes

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