Ammonia → HCID 15219011, compound

HRID 1743069Notes

Reaction equation

HRID 1743069 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)[C@H:13]1[O:18][C:16](=[O:17])[C@H:15]([CH:19]([CH3:21])[CH3:20])[CH2:14]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[Cl-].[Ca+2].[BH4-].[Na+].N>C(O)C.C1COCC1.C(OCC)C.C(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C@@H:13]([OH:18])[CH2:14][C@@H:15]([CH:19]([CH3:20])[CH3:21])[CH2:16][OH:17])[CH2:22][CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 222AmmoniaHCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 18637741(2S,4S,5S)-5-benzyloxycarbonylamino-6-cyclohexyl-2-isopropyl-4-hexanolide

Product 1

HCID 15219011HCID 15219011, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To (2S,4S,5S) -5-benzyloxycarbonylamino-6-cyclohexyl-2-isopropyl-4-hexanolide (J. Med. Chem. 31, 1839-46 (1988), 3.88 g, 10.0 mmol) and CaCl2 (2.22 g, 20.0 retool) dissolved in a mixture of 60 mL ethanol and 60 mL THF and cooled to 0° C. was added portionwise NaBH4 (1.5 g, 40.0 mmol) resulting in vigorous gas evolution and an exotherm. The resulting solution was stirred at 0° C. for 1 hour and then at ambient temperature for 1 hour, diluted with 100 mL of diethyl ether and filtered through a plug of Celite®. The filtrate was cooled to 0° C. and quenched by the addition of 1M KHSO4 until bubbling ceased. The organic phase was washed with 2×20 mL of saturated NaHCO3 and 2×20 mL of saturated brine, dried (MgSO4) and concentrated in vacuo to a give a white solid. Recrystallization from EtOAc/hexanes gave 3.67 g (94%) of the (2S,3S,5S) -diastereomer. m.p. 113°-114° C. [α]25D =-32.0° (c=1.025, CHCl3). 1H NMR (C6D6, 300 MHz) δ0.76 (d, J=7.5Hz, 3H), 0.79 (d, J=7.5Hz, 3H), 0.75-1.74 (complex m, 18H), 1.98-2.09 (bd, J=11.1Hz, 1 H), 3.28-3.41 (m, 2H), 3.62-3.70 (m, 1H), 3.90-4.00 (m, 1H), 4.88 (d, J=9.6Hz, 1H), 5.12 (s, 2H), 7.00-7.30 (m, 5H). MS (DCI/NH3) 392 (M+H)+, 409 (M+NH4)+. Analysis calcd for C23H37NO4 : C, 70.55; H, 9.52; N, 3.58. Found: C, 70.78; H, 9.54; N, 3.56.

Workup

  1. customresulting in vigorous gas evolution
  2. waitat ambient temperature for 1 hour
  3. filtrationfiltered through a plug of Celite®
  4. temperatureThe filtrate was cooled to 0° C.
  5. customquenched by the addition of 1M KHSO4
  6. customuntil bubbling
  7. washThe organic phase was washed with 2×20 mL of saturated NaHCO3 and 2×20 mL of saturated brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo to
  10. customa give a white solid
  11. customRecrystallization from EtOAc/hexanes
  12. customgave 3.67 g (94%) of the (2S,3S,5S) -diastereomer

Sources & evidence

ORD record
ord-1b7a1b0ee54e47e0aa3db2e28cfa4f7f
Source dataset
uspto-grants-1994_08
Patent number
US05342981

Reaction notes

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