Triethylamine → 4-[1-(5-Hydroxymethyl-4-trifluoromethyl-pyrimidin-2-yl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 2066876Notes

Reaction equation

HRID 2066876 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][N:14]=[C:15]2[CH2:20][CH2:19][N:18]([C:21]3[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[C:24]([C:31](O)=[O:32])=[CH:23][N:22]=3)[CH2:17][CH2:16]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>C1COCC1.O>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([O:13][N:14]=[C:15]2[CH2:16][CH2:17][N:18]([C:21]3[N:26]=[C:25]([C:27]([F:30])([F:28])[F:29])[C:24]([CH2:31][OH:32])=[CH:23][N:22]=3)[CH2:19][CH2:20]2)[CH2:11][CH2:12]1)=[O:6])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 866550162-[4-(1-Isopropoxycarbonyl-piperidin-4-yloxyimino)-piperidin-1-yl]-4-trifluoromethyl-pyrimidine-5-carboxylic acid

Product 1

HCID 583336184-[1-(5-Hydroxymethyl-4-trifluoromethyl-pyrimidin-2-yl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Half of the crude 57b was combined with triethylamine (50 μL, 0.36 mmol) in 2 mL of THF and treated at 0° C. with ethyl chloroformate (30 μL, 0.31 mmol). The mix was stirred at room temperature for 4 h then it was added to a stirred suspension of sodium borohydride (32 mg, 0.84 mmol) in water and the stirring was continued for 3 h. The mixture was quenched with aqueous NaHCO3 (5 mL) and water (5 mL) and extracted with EtOAc (3×5 mL). The combined extracts were dried and concentrated and the residue was purified by preparative HPLC to afford 58-1: LC-MS 460.1 (MH+), tR=7.49 (Method 2).

Workup

  1. waitthe stirring was continued for 3 h
  2. customThe mixture was quenched with aqueous NaHCO3 (5 mL) and water (5 mL)
  3. extractionextracted with EtOAc (3×5 mL)
  4. customThe combined extracts were dried
  5. concentrationconcentrated
  6. customthe residue was purified by preparative HPLC
  7. customto afford 58-1

Sources & evidence

ORD record
ord-8aeaaf376d61416b906d1111789614db
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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