Water → tert-butyl N-(4-chloro-3-(hydroxymethyl)phenyl)carbamate

HRID 1760025Notes

Reaction equation

NC1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C[N:13]([CH:15]=[O:16])[CH3:14].ClC(O[CH2:21][CH:22]([CH3:24])[CH3:23])=O.[BH4-].[Na+].[OH2:27]>>[Cl:11][C:5]1[CH:4]=[CH:3][C:14]([NH:13][C:15]([O:16][C:22]([CH3:24])([CH3:23])[CH3:21])=[O:27])=[CH:10][C:6]=1[CH2:7][OH:9]

Participants

Reactant 5

HCID 962Water2×

HCID 6228Dimethylformamide

HCID 378795-Amino-2-chlorobenzoic acid

HCID 62365Isobutyl chloroformate

HCID 4311764Sodium borohydride

Product 1

HCID 54223790tert-butyl N-(4-chloro-3-(hydroxymethyl)phenyl)carbamateYield 87%

Conditions

Temperature: -15 °C

Procedure

To an ice-cold solution of 5-amino-2-chlorobenzoic acid (9.0 g; 33 mmol) in THB:DMF (200 mL; 1:1) was added TEA (4.0 g; 40 mmol), followed by isobutyl chloroformate (5.4 g; 40 mmol; added dropwise). The mixture was then stirred for another 30 minutes, the white precipitate formed was removed by filtration, the filtrate was cooled to −15° C., and NaBH4 (3.8 g; 100 mmol) and water (20 mL) were added. After 15 minutes, water (200 mL) was added and the solution was stirred at room temperature for 1 hour. After evaporation, the residue was dissolved in MeOH. Filtration and concentration gave the crude product which was purified by flash chromatography (Si-gel, CH2Cl2:MeOH (9:1)) resulting in 7.4 g (87%) of the subtitle compound.

Workup

additionadded dropwise)
customthe white precipitate formed
customwas removed by filtration
waitAfter 15 minutes
stirringthe solution was stirred at room temperature for 1 hour
customAfter evaporation
dissolutionthe residue was dissolved in MeOH
filtrationFiltration and concentration
customgave the crude product which
customwas purified by flash chromatography (Si-gel, CH2Cl2:MeOH (9:1))

Sources & evidence

ORD record: ord-28a963ce34aa45e78bcf5cff74da4403
Source dataset: uspto-grants-2005_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06838478B2

Reaction notes

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