Benzyl Bromide → Dicyclohexylamine

HRID 1285098Notes

Reaction equation

HRID 1285098 reaction equation
[C:1]([NH:9][C@@H:10]([C:16](O)=O)[CH2:11][CH2:12][C:13](O)=O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]C.[CH2:19](N(CC)CC)C.C(Br)C1C=CC=CC=1.C(OCC)(=O)C>CN(C)C=O>[CH:10]1([NH:9][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:11][CH2:12][CH2:13][CH2:19][CH2:16]1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 13851772HCID 13851772, compound

Product 1

HCID 7582DicyclohexylamineYield 64.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 108.8 g (420 mmol) of N-heptanoyl-D-glutamic acid and 50.6 g (500 mmol) of triethylamine in 135 ml of dimethylformamide was treated with 85.7 g (500 mmol) of benzyl bromide and stirred under nitrogen atmosphere for 60 hours. The reaction was poured onto one liter of ethyl acetate and washed successively with two 500 ml portions each of dilute hydrochloric acid and water. The ethyl acetate was then washed with 500 ml of 1N sodium hydroxide. The basic aqueous layer was acidified with dilute acid and extracted with four 500 ml portions of ethyl acetate. The combined ethyl acetate extracts were treated with excess dicyclohexylamine and stirred 18 hours. The suspension was filtered, slurried in fresh ethyl acetate (400 ml) for two hours, refiltered and dried under vacuum to give 49.1 g of dicyclohexylamine salt. The resulting salt (14.0 g) was stirred in dilute hydrochloric acid, filtered and washed with ethyl acetate. The aqueous filtrate was extracted twice with ethyl acetate, and the organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting oil was triturated with hexane to give 7.9 g (86% from salt) of the title ester: mp 76°-79° C.; IR (Nujol) 3300, 2700-3100, 1730, 1700, 1645 cm-1 ; NMR (CDCl3) delta 7.35 (s, 5H), 5.20 (s, 2H), 4.70 (m, 1H), 1.85-2.50 (m, 6H), 1.55-1.70 (m, 2H), 1.10-1.40 (m, 6H), 0.75 (t, 3H); [alpha]D =27.6 (C=0.6, MeOH).

Workup

  1. washwashed successively with two 500 ml portions each of dilute hydrochloric acid and water
  2. washThe ethyl acetate was then washed with 500 ml of 1N sodium hydroxide
  3. additionwith dilute acid
  4. extractionextracted with four 500 ml portions of ethyl acetate
  5. additionThe combined ethyl acetate extracts were treated with excess dicyclohexylamine
  6. stirringstirred 18 hours
  7. filtrationThe suspension was filtered
  8. waitslurried in fresh ethyl acetate (400 ml) for two hours
  9. customdried under vacuum

Sources & evidence

ORD record
ord-843e512859cb46eb9e6b737dbbda39cd
Source dataset
uspto-grants-1986_01
Patent number
US04565653

Reaction notes

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