Carbon tetrabromide → tert-Butyl N-[3-(bromomethyl)benzyl]-N-methylcarbamate

HRID 567804Notes

Reaction equation

HRID 567804 reaction equation
[C:1]([O:5][C:6](=[O:18])[N:7]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16]O)[CH:11]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:20][CH2:16][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][CH:13]=1)[CH2:9][N:7]([CH3:8])[C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 18470938tert-Butyl 3-(hydroxymethyl)benzyl(methyl)carbamate

Product 1

HCID 18470889tert-Butyl N-[3-(bromomethyl)benzyl]-N-methylcarbamateYield 63.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A milky suspension of 3-[(methylamino)methyl]phenylmethanol (preparation 12) (2.7 g, 17.9 mmol) in THF (60 ml) and water (60 ml) was treated with di-t-butylpyrocarbonate (5.4 g,24.7 mmol) and the mixture stirred at room temperature overnight. The THF was evaporated and the aqueous residue treated with ethyl acetate (250 ml). The organic layer was washed with sat aq brine (100 ml) a and dried over MgSO4. Filtration away from the drying agent followed by evaporation of the solvent gave the crude product which was purified by chromatography (SiO2, eluting with 95:5CH2Cl2:MeOH) to give the intermediate tert-butyl N-[3-(hydroxymethyl)benzyl]-N-methylcarbamate(4.2 g) which was used directly in the next step. A stirred solution of tert-butyl-N-[3-(hydroxymethyl)benzyl]-N-methylcarbamate (4.2 g, 16.7 mmol) in CH2Cl2 (150 ml) at 0° C., was treated with carbon tetrabromide (8.0 g, 24.1 mmol) and triphenyl phosphine (6.35 g, 24.21 mmol). The resultant solution was warmed to room temperature and stirred for 4 days. The resultant mixture was evaporated to dryness and the residue purified by chromatography (SiO2, gradient elution with 100% hexane; 99:1 hexane:ethyl acetate; 95:5 hexane:ethyl acetate) to give the desired product (3.32 g, 60%). 1H NMR (CDCl3) δ 1.50 (s, 9H), 2.80 (s, br, 3H), 4.20 (s, 2H), 4.30 (s, 2H), 7.15 (m, 1H), 7.25 (m, 1H), 7.30 (m, 2H). LRMS m/z=333.2 (M+18)+.

Workup

  1. customThe resultant mixture was evaporated to dryness
  2. customthe residue purified by chromatography (SiO2, gradient elution with 100% hexane; 99:1 hexane:ethyl acetate; 95:5 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-8167a43eeaf744c5acb4ed2c591719f0
Source dataset
uspto-grants-2001_01
Patent number
US06180627B2

Reaction notes

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