Triethylamine → tert-Butyl [4-(hydroxymethyl)benzyl]carbamate

HRID 2186048Notes

Reaction equation

HRID 2186048 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([CH2:14][OH:15])=[CH:17][CH:18]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 4311764Sodium borohydride

Product 1

HCID 2794813tert-Butyl [4-(hydroxymethyl)benzyl]carbamateYield 65.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-[N-(t-butoxycarbonyl)-aminomethyl]benzoic acid (16.5 g, 65 mmol) and triethylamine (10 mL, 71 mmol) in dry THF (500 mL) at 0° C. was added ethyl chloroformate (7.5 mL, 78 mmol) dropwise. After stirring for 15 min, sodium borohydride (6 g, 159 mmol) was added in one portion and the reaction was allowed to warm to RT and stirred for 16 h. The reaction was cooled in an ice bath and carefully quenched with 1N hydrochloric acid, extracted with ethyl acetate, and the organic phase was washed with brine, dried (magnesium sulfate), and concentrated. The residue was purified by flash chromatography (silica gel, 20% ethyl acetate:chloroform) to give the title compound (10.07 g, 65%) as a white solid. TLC Rf 0.31 (20% ethyl acetate:chloroform); 1H NMR (CDCl3) δ1.46 (9H, s), 3.28 (1H, br s), 4.27 (2H, d, J=6 Hz), 4.65 (2H, s), 5.04 (1H, br s), 7.30 (4H, dd).

Workup

  1. stirringstirred for 16 h
  2. temperatureThe reaction was cooled in an ice bath
  3. customcarefully quenched with 1N hydrochloric acid
  4. extractionextracted with ethyl acetate
  5. washthe organic phase was washed with brine
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (silica gel, 20% ethyl acetate:chloroform)

Sources & evidence

ORD record
ord-5c0fd247f0e142ce91f8e75fa5554a55
Source dataset
uspto-grants-2002_06
Patent number
US06403578B1

Reaction notes

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