(+)-Epichlorohydrin → (2S,9S)-2-[(tert-Butoxycarbonyl)amino]-10-chloro-9-hydroxy-7-azadecanoic Acid tert-Butyl Ester

HRID 1068073Notes

Reaction equation

HRID 1068073 reaction equation
Cl.[C:2]([O:6][C:7](=[O:22])[C@H:8]([CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])[NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:5])([CH3:4])[CH3:3].[CH2:23]([C@H:25]1[O:27][CH2:26]1)[Cl:24]>C(Cl)(Cl)Cl.C([O-])(O)=O.[Na+].O>[C:2]([O:6][C:7](=[O:22])[C@@H:8]([NH:9][C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:26][C@H:25]([OH:27])[CH2:23][Cl:24])([CH3:5])([CH3:3])[CH3:4]

Participants

6

Reactant 2

HCID 149428(+)-EpichlorohydrinHCID 513584377750-45-0

Product 1

HCID 10810670(2S,9S)-2-[(tert-Butoxycarbonyl)amino]-10-chloro-9-hydroxy-7-azadecanoic Acid tert-Butyl EsterYield 39%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 3 (4.83 g, 14.3 mmol) in chloroform (100 mL) was extracted with saturated NaHCO3 solution (2×100 mL) and water (100 mL). The organic layer was dried, concentrated, and further dried in vacuo. The resulting oil was dissolved in cyclohexane (26 mL), and (S)-(+)-epichlorohydrin (1.58 g, 17.1 mmol) was added under an Ar atmosphere. The precipitated product was filtered after 27 h, washed with cold cyclohexane, and dried in vacuo to give 12a (2.20 g, 39%) as a fine, white powder: mp 87-88° C.; 1H NMR δ 1.30-1.83 (m, 6H), 1.44 (s, 9H), 1.46 (s, 9H), 2.57-2.66 (m, 3H), 2.77 (dd, 1H, J=12.2, 3.9), 3.51 (dd, 1H, J=11.2, 5.7), 3.56 (dd, 1H, J=11.2, 5.2), 3.84-3.91 (m, 1H), 3.94 (dd, 1H, J=8.6, 5.3); 13C NMR 6 24.6, 28.3, 28.7, 30.0, 32.6, 48.2, 50.3, 53.5, 55.8, 71.1, 80.4, 82.5, 158.1, 173.8; HRMS m/z calcd for C18H36ClN2O5 395.2313, found 395.2303. Anal. calcd. for C18H35ClN2O5: C54.74, H 8.93, Cl 8.98, N 7.09. Found: C 54.80, H. 8.99, Cl 9.02, N 7.08 [α]22D−26.1° (c 1.00, CH3OH).

Workup

  1. customThe organic layer was dried
  2. concentrationconcentrated
  3. customfurther dried in vacuo
  4. dissolutionThe resulting oil was dissolved in cyclohexane (26 mL)
  5. filtrationThe precipitated product was filtered after 27 h
  6. washwashed with cold cyclohexane
  7. customdried in vacuo

Sources & evidence

ORD record
ord-447e88a649b64535b55e347f884d4418
Source dataset
uspto-grants-2001_06
Patent number
US06248866B1

Reaction notes

Loading…