4-Methylmorpholine → HCID 178432701, compound

HRID 1670661Notes

Reaction equation

HRID 1670661 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C@H:16]3[CH2:21][CH2:20][C@H:19]([CH2:22][C:23](O)=[O:24])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[C:7]([CH3:26])=[N:6][C:5]=1[CH3:27])(=[O:3])[NH2:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.O>[OH:24][CH2:23][CH2:22][C@H:19]1[CH2:18][CH2:17][C@H:16]([C:13]2[CH:14]=[CH:15][C:10]([C:8]3[N:9]=[C:4]([C:1]([NH2:2])=[O:3])[C:5]([CH3:27])=[N:6][C:7]=3[CH3:26])=[CH:11][CH:12]=2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformate2×HCID 4311764Sodium borohydrideHCID 178432703HCID 178432703, compound

Product 1

HCID 178432701HCID 178432701, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of Example 1 (50 mg, 0.14 mmol) and NMM (71 μL, 0.64 mmol) in THF (1 mL) at 0° C. was added a solution of ethyl chloroformate (61 μL, 0.64 mmol) in THF (0.5 mL). The reaction was stirred at 0° C. for ˜3 h, but additional equivalents of NMM and ethyl chloroformate were needed during this time to drive the reaction. The reaction mixture was added dropwise to a solution of NaBH4 in water at 0-5° C. and the combined mixture was stirred for 30 min. The mixture was partitioned between EtOAc and 1M HCl and the organic layer was washed with water, dried through a phase separator and concentrated. The crude was dissolved in DMSO and purified by HPLC (neutral). Freeze-drying of pure fractions gave the title compound (8 mg, 17%) as white powder.

Workup

  1. customthe reaction
  2. stirringthe combined mixture was stirred for 30 min
  3. customThe mixture was partitioned between EtOAc and 1M HCl
  4. washthe organic layer was washed with water
  5. customdried through a phase separator
  6. concentrationconcentrated
  7. dissolutionThe crude was dissolved in DMSO
  8. custompurified by HPLC (neutral)
  9. customFreeze-drying of pure fractions

Sources & evidence

ORD record
ord-9f63de175917456587cc399576f0cd8c
Source dataset
uspto-grants-2011_08
Patent number
US07994179B2

Reaction notes

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