Benzylamine → HCID 71283397, compound

HRID 2276647Notes

Reaction equation

HRID 2276647 reaction equation
[CH2:1]([N:8]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@H:9]([CH2:13][OH:14])[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[CH2:32]([NH2:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CCN=C=NCCCN(C)C.Cl>ClCCl.C(N(CC)CC)C>[CH2:32]([NH:39][C:10](=[O:11])[C@H:9]([N:8]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:13][OH:14])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68418712HCID 68418712, compound

Product 1

HCID 71283397HCID 71283397, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
22.5 °C

Procedure

To the suspension of (R)-2-(dibenzylamino)-3-hydroxypropanoic acid (285.34 g, 1.0 moL) in dichloromethane (2.86 L) was added HOBt (202.68 g, 1.50 moL), triethylamine (111.31 g, 1.1 moL), benzyl amine (117.86 g 1.1 moL) and EDC.HCl (230.04 g, 1.2 moL) at 0-5° C. under constant stirring. The reaction mixture was stirred at below 10° C. for 16 hours. When the reaction was considered complete, the agitation was stopped and the phases were allowed to separate. The organic phase was washed with water (856 mL), saturated sodium bicarbonate (2×713 mL), water (713 mL) and finally with a mixture of 2.85 mL of 30% HCl and 570 mL of water. The organic phase was concentrated under reduced pressure to a final volume of about 485 mL. MTBE (770 mL) was added and distilled again under reduced pressure to a final volume of about 485 mL. The reaction mixture was cooled to 20-25° C., and charged with heptanes (856 mL). The reaction mixture was heated to 28-32° C. and stirred for 1 hour, then cooled to 0-5° C. and stirred for 3 hours. The obtained mixture was filtered and the cake was washed with cold (0-5° C.) heptanes (285 mL). The resulting solid was dried under vacuum at 45-50° C. for 12 hours to provide (R)—N-benzyl-2-(dibenzylamino)-3-hydroxypropanamide as a white solid (353.82 g, yield 95%, HPLC purity >99.95%).

Workup

  1. customto separate
  2. washThe organic phase was washed with water (856 mL), saturated sodium bicarbonate (2×713 mL), water (713 mL) and finally with a mixture of 2.85 mL of 30% HCl and 570 mL of water
  3. concentrationThe organic phase was concentrated under reduced pressure to a final volume of about 485 mL
  4. additionMTBE (770 mL) was added
  5. distillationdistilled again under reduced pressure to a final volume of about 485 mL
  6. additioncharged with heptanes (856 mL)
  7. temperatureThe reaction mixture was heated to 28-32° C.
  8. stirringstirred for 1 hour
  9. temperaturecooled to 0-5° C.
  10. stirringstirred for 3 hours
  11. filtrationThe obtained mixture was filtered
  12. washthe cake was washed with cold (0-5° C.) heptanes (285 mL)
  13. customThe resulting solid was dried under vacuum at 45-50° C. for 12 hours

Sources & evidence

ORD record
ord-d9853317371148cd9e702785119f5d5b
Source dataset
uspto-grants-2015_09
Patent number
US09133101B2

Reaction notes

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