Triethylamine → HCID 131710209, compound

HRID 1076418Notes

Reaction equation

HRID 1076418 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.C(OC(Cl)=O)C(C)C.[NH2:38][C@H:39]([C:46]([O:48][CH3:49])=[O:47])[CH2:40][O:41][C:42]([CH3:45])([CH3:44])[CH3:43].Cl.Cl.C(N(CC)CC)C>O1CCCC1>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([NH:38][C@H:39]([C:46]([O:48][CH3:49])=[O:47])[CH2:40][O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 11130Triethylamine hydrochlorideHCID 62365Isobutyl chloroformateHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 16218549Methyl O-tert-butyl-L-serinate--hydrogen chloride (1/1)

Product 1

HCID 131710209HCID 131710209, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

27.0 g (90 mmols) of Z-Phe-OH are dissolved in 250 ml of absolute tetrahydrofurane together with 12.5 ml (90 mmols) of triethylamine, and cooled. 14.7 ml (112 mmols) of chlorocarbonic acid isobutyl ester are added dropwise at -18°C and the mixture is stirred for one-half an hour at <-10°C. 18.1 g of H-Ser(tBu)-OCH3 hydrochloride (85.5 mmols) in a finely powdered form are now added to the white suspension (triethylamine hydrochloride), the mixture is diluted with 350 ml of tetrahydrofurane, and 15.0 m (108 mmols) of triethylamine in 100 ml of tetrahydrofurane are then added dropwise. The mixture is stirred for a further 3 hours at about -10°C and then overnight at room temperature. The suspension is then concentrated to about 250 ml in vacuo, taken up in a large amount of ethyl acetate and extracted by shaking with dilute citric acid solution (3 × 200 ml), dilute sodium carbonate solution (3 × 200 ml) and saturated sodium chloride solution (5 × 200 ml), dried over sodium sulphate and evaporated. The crude product is dissolved in 200 ml of ethyl acetate-hexane (1 : 1). White husks crystallise out of the solution on cooling and these are isolated and dried. The product melts at 92.5°- 94°C. [α]D20 = 3° ± 0.5° (c = 2.2 % in methanol).

Workup

  1. temperaturecooled
  2. additionare then added dropwise
  3. stirringThe mixture is stirred for a further 3 hours at about -10°C
  4. customovernight
  5. customat room temperature
  6. concentrationThe suspension is then concentrated to about 250 ml in vacuo
  7. extractionextracted
  8. stirringby shaking with dilute citric acid solution (3 × 200 ml), dilute sodium carbonate solution (3 × 200 ml) and saturated sodium chloride solution (5 × 200 ml)
  9. dry with materialdried over sodium sulphate
  10. customevaporated
  11. dissolutionThe crude product is dissolved in 200 ml of ethyl acetate-hexane (1 : 1)
  12. customWhite husks crystallise out of the solution
  13. temperatureon cooling
  14. customthese are isolated
  15. customdried

Sources & evidence

ORD record
ord-08d28627c34a496f979113875ce6f7d2
Source dataset
uspto-grants-1976_05
Patent number
US03956260

Reaction notes

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