Sodium Hydroxide → (2R)-N-(Benzyloxy)-2-(hydroxymethyl)hexanamide

HRID 733480Notes

Reaction equation

HRID 733480 reaction equation
[OH:1][CH2:2][C@@H:3]([CH2:7][CH2:8][CH2:9][CH3:10])[C:4]([OH:6])=O.Cl.[CH2:12]([O:19][NH2:20])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+].Cl.CN(C)CCCN=C=NCC>O>[OH:1][CH2:2][C@@H:3]([CH2:7][CH2:8][CH2:9][CH3:10])[C:4]([NH:20][O:19][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:6]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 102312Benzyloxyamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11550035(2R)-2-(hydroxymethyl)hexanoic Acid

Product 1

HCID 16037944(2R)-N-(Benzyloxy)-2-(hydroxymethyl)hexanamideYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
16.5 °C

Procedure

A 5 L, 4-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer and nitrogen inlet-outlet, is charged with 102.39 g of (2R)-2-(hydroxymethyl)hexanoic acid, 123.0 g of O-benzylhydroxylamine hydrochloride and 2.25 L of water. Adjust the pH by adding one equivalent of NaOH to a pH of 4-5. Stir the reaction mixture at 18° C.±3° C. (external temperature: 15-18° C.) for 30 minutes to give a cloudy solution. Add 161.3 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCl) over a period of 60 minutes in 6 portions, while maintaining the internal temperature at 18° C.±3° C. (external temperature: 10° C.±3° C.). Wash the funnel once with 50 mL of water. Stir the thick suspension at 20° C.±3° C. for 2 hours. Filter the solids through a polypropylene filter cloth and a Büchner funnel then wash the flask and filter cake once with 0.5 L of water. Air-dry the cake at 20° C.±3° C. (house vacuum) for 2 hours, then dry the wet cake (˜265 g weight) at 65° C.±3° C. (15 mbar) for 24 hours to give 162 g of (2R)-2-(hydroxymethyl)-N-(phenylmethoxy)hexanamide (C3) as a white solid in 95% yield. m.p. 100-102° C.; [α]D25=+0.556 (c, 1.0, MeOH).

Workup

  1. customA 5 L, 4-necked, round-bottomed flask, equipped with a mechanical stirrer
  2. customto give a cloudy solution
  3. temperaturewhile maintaining the internal temperature at 18° C.±3° C. (external temperature: 10° C.±3° C.)
  4. washWash the funnel once with 50 mL of water
  5. stirringStir the thick suspension at 20° C.±3° C. for 2 hours
  6. filtrationFilter the solids through a polypropylene
  7. filtrationfilter cloth
  8. washa Büchner funnel then wash the flask
  9. filtrationfilter cake once with 0.5 L of water
  10. customAir-dry the cake at 20° C.±3° C. (house vacuum) for 2 hours
  11. customdry the wet cake (˜265 g weight) at 65° C.±3° C. (15 mbar) for 24 hours

Sources & evidence

ORD record
ord-c603dbc9c2bf4359b42bde263b63cb54
Source dataset
uspto-grants-2009_09
Patent number
US07589216B2

Reaction notes

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