Triethylamine → HCID 131714445, compound

HRID 986773Notes

Reaction equation

HRID 986773 reaction equation
[C:1]([NH:9][C@@H:10]([CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:11][P:12]([CH2:15][C:16]([OH:18])=O)([OH:14])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)CC)C.Cl.[NH:43]1[CH2:57][CH2:56][CH2:55][C@H:44]1[C:45]([O:47][CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:46].[NH4+].[OH-].O>O1CCCC1.C(O)(C)C.C(O)(=O)C.CO.ClCCl>[C:1]([NH:9][CH:10]([CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:11][P:12]([CH2:15][C:16]([N:43]1[CH2:57][CH2:56][CH2:55][C@H:44]1[C:45]([O:47][CH2:48][C:49]1[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1)=[O:46])=[O:18])([OH:14])=[O:13])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 2733413Proline benzyl ester hydrochlorideHCID 54211279HCID 54211279, compoundHCID 86589665Water ammonium hydroxide

Product 1

HCID 131714445HCID 131714445, compound

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 21877243DCM MeOH AcOHSolvent

Procedure

A solution of (S)-[[2-(benzoylamino)-4-methylpentyl]hydroxyphosphinyl]acetic acid (0.85 g., 2.60 mmole) in dry tetrahydrofuran (10 ml.) at 0° (ice bath) under argon was treated with carbonyldiimidazole (0.50 g., 3.08 mmole). After one hour, the mixture was treated with triethylamine (1.0 ml., 7.23 mmole), and L-proline, phenylmethyl ester, hydrochloride salt (0.75 g., 3.1 mmole), allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between ethyl acetate-5% potassium bisulfate. The ethyl acetate layer was washed successively with 5% potassium bisulfate, 5% sodium biphosphate (pH 4.5 buffer) and saturated sodium chloride, dried (MgSO4) and evaporated. The residue (1.3 g.) was taken up in 1N lithium hydroxide (2.5 ml.), diluted with saturated sodium bicarbonate (30 ml.) and washed with ether (twice). The aqueous phase was acidified with concentrated hydrochloric acid (pH 1) and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with saturated sodium chloride, dried (MgSO4) and evaporated to give 0.9 g. of (S)-1-[[[2-(benzoylamino-4-methylpentyl]hydroxyphosphinyl]acetyl]-L-proline, phenylmethyl ester as a white foam. Rf (acetic acid/methanol/dichloromethane; 1:1:20)=0.25; Rf (isopropanol/conc. NH4OH/water; 7:2:1)=0.74.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate-5% potassium bisulfate
  2. washThe ethyl acetate layer was washed successively with 5% potassium bisulfate, 5% sodium biphosphate (pH 4.5 buffer) and saturated sodium chloride
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. additiondiluted with saturated sodium bicarbonate (30 ml.)
  6. washwashed with ether (twice)
  7. extractionextracted with ethyl acetate
  8. washThe combined ethyl acetate extracts were washed with saturated sodium chloride
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customto give 0.9 g

Sources & evidence

ORD record
ord-89a3cfcb9a0847b591c19c035c12b974
Source dataset
uspto-grants-1987_12
Patent number
US04716155

Reaction notes

Loading…