4-Methylmorpholine → HCID 22730679, compound

HRID 1785862Notes

Reaction equation

HRID 1785862 reaction equation
[CH3:1][C:2]1([C:39](O)=[O:40])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][CH2:27][CH2:28][S:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[C:22]([N+:36]([O-:38])=[O:37])[CH:21]=3)(=[O:19])=[O:18])=[O:15])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>O.COCCOC>[OH:40][CH2:39][C:2]1([CH3:1])[CH2:3][CH2:4][N:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][S:17]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][CH2:27][CH2:28][S:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[C:22]([N+:36]([O-:38])=[O:37])[CH:21]=3)(=[O:19])=[O:18])=[O:15])=[CH:10][CH:9]=2)[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 22730642HCID 22730642, compound

Product 1

HCID 22730679HCID 22730679, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of Example 532H (35 mg, 0.06 mmol), 4-methylmorpholine (0.007 mL, 0.06 mmol), and DME (0.3 mL) at −15° C. was treated dropwise with isobutyl chloroformate (0.008 mL, 0.06 mmol), stirred for 15 minutes, and filtered. The filter cake was washed with DME and the filtrate and washings were combined. The solution was cooled to −15° C., treated sequentially with NaBH4 (3.5 mg, 0.09 mmol) water (0.03 mL), and additional water (50 mL), and extracted with dichloromethane. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated The concentrate was purified by flash column chromatography on silica gel with 1-2% methanol/dichloromethane to provide the desired product. MS (ESI(−))) m/e 583 (M−H)−; 1H NMR (500 MHz, DMSO-d6) δ 11.92 (s, 1H), 8.75 (t, 1H), 8.58 (d, 1H), 7.90 (dd, 1H), 7.72 (d, 2H), 7.38 (d, 2H), 7.27 (t, 2H), 7.15 (m, 2H), 6.90 (d, 2H), 4.53 (t, 1H), 3.66 (m, 2H), 3.50 (m, 2H), 3.30 (m, 2H), 3.16 (m, 4H), 1.50 (m, 2H), 1.25 (m, 2H), 0.91 (s, 3H).

Workup

  1. filtrationfiltered
  2. washThe filter cake was washed with DME
  3. extractionextracted with dichloromethane
  4. washThe combined extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated The concentrate
  8. customwas purified by flash column chromatography on silica gel with 1-2% methanol/dichloromethane

Sources & evidence

ORD record
ord-5ac43e5e93c54008ba4c942b6b3598b4
Source dataset
uspto-grants-2009_03
Patent number
US07504512B2

Reaction notes

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