4-Methylmorpholine → HCID 40428773, compound

HRID 352707Notes

Reaction equation

HRID 352707 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:29](O)=[O:30])[CH2:20][CH:21](C(C)(C)C)[C:22]([OH:24])=[O:23])=[O:17])[C:11]3C(=CC=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.ClC(O[CH2:43][CH:44]([CH3:46])[CH3:45])=O.[BH4-].[Na+].[CH2:49]1[CH2:53]OC[CH2:50]1>CO>[C:44]([O:24][C:22](=[O:23])[CH2:21][CH2:20][C@H:19]([NH:18][C:16]([O:15][CH2:14][CH:12]1[C:13]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[C:53]2[C:11]1=[CH:10][CH:9]=[CH:50][CH:49]=2)=[O:17])[CH2:29][OH:30])([CH3:46])([CH3:45])[CH3:43]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 8028Tetrahydrofuran2×HCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 22975989HCID 22975989, compound

Product 1

HCID 40428773HCID 40428773, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-(9-fluorenylmethoxycarbonyl)-γ-t-butyl glutamic acid (8.51 g, 20.0 mmol) and NMM (2.42 mL, 1.1 eq) in dry THF (110 mL) under N2 at 0° C. was added isobutyl chloroformate (2.72 mL, 1.05 eq). After 20 min., the reaction e was filter-added to a solution of NaBH4 (1.5 g) in THF (120 mL)-MeOH (30 mL) at −78° C. under N2 and rinsed with dry THF (20 mL). After stirring for 2.5 h at −78° C., the reaction was quenched with acetic acid (13 mL). After concentrating to ˜50 mL, the residue was dissolved in ethyl acetate-hexanes (200 mL, 1:1), washed with water (150 mL×2). Aqueous layer was re-extracted with ethyl acetate-hexanes (150 mL, 1:1). Combined extract was washed with sat'd NaHCO3 (150 mL×2), dried (anhydrous Na2SO4), filtered and concentrated to give 8.30 g of the title compound as glasslike solid. The crude alcohol was used directly.

Workup

  1. washrinsed with dry THF (20 mL)
  2. customthe reaction was quenched with acetic acid (13 mL)
  3. concentrationAfter concentrating to ˜50 mL
  4. dissolutionthe residue was dissolved in ethyl acetate-hexanes (200 mL, 1:1)
  5. washwashed with water (150 mL×2)
  6. extractionAqueous layer was re-extracted with ethyl acetate-hexanes (150 mL, 1:1)
  7. extractionCombined extract
  8. washwas washed with sat'd NaHCO3 (150 mL×2)
  9. dry with materialdried (anhydrous Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c47413fc6ccf42c98fbab91b3ded6650
Source dataset
uspto-grants-2004_06
Patent number
US06747050B1

Reaction notes

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