tert-Butyl bromoacetate → 4-{[N-(boc)methylamino]methyl}phenol

HRID 923559Notes

Reaction equation

HRID 923559 reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Br[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]>CN(C=O)C.CC(=O)OCC>[OH:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH:1][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:5]=1

Participants

5

Reactant 2

HCID 79177tert-Butyl bromoacetateHCID 974724-Hydroxybenzylamine

Product 1

HCID 538343224-{[N-(boc)methylamino]methyl}phenolYield 48.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 13: To a stirred solution of 4-(aminomethyl)phenol (2.0 g, 16.2 mmol) in DMF (10 mL) was added TEA (4.53 mL, 32.5 mmol) followed by tert-butyl 2-bromoacetate (2.40 mL, 16.2 mmol) added drop-wise over 30 minutes. After stirring a further 1 h at room temperature, the reaction mixture was diluted with EA (100 mL) and washed with water (2×100 mL). The organics were isolated and pre-absorbed onto silica gel then purified by silica gel chromatography (EA/isohexanes) to afford 1.86 g (48%) tert-butyl 2-((4-hydroxybenzyl)amino)acetate INT-22 as a white powder. LCMS-ESI (m/z) calculated for C13H19NO3: 237 found 236 [M−H]−, tR=1.20 min (Method 10). 1H NMR (400 MHz, DMSO) δ 9.24 (s, 1H), 7.12-7.05 (m, 2H), 6.73-6.66 (m, 2H), 3.55 (s, 2H), 3.12 (s, 2H), 2.15 (s, 1H) 1.41 (s, 9H).

Workup

  1. customPrepared
  2. additionadded drop-wise over 30 minutes
  3. washwashed with water (2×100 mL)
  4. customThe organics were isolated
  5. custompre-absorbed onto silica gel
  6. customthen purified by silica gel chromatography (EA/isohexanes)

Sources & evidence

ORD record
ord-e6628cd20a5d4e9c95395c313ac055c4
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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