Ethyl Acetate → 3-[4-Methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester

HRID 519086Notes

Reaction equation

HRID 519086 reaction equation
C([O-])([O-])=O.[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16]([NH:18][C:19]2[CH:20]=[C:21]3[C:30](=[CH:31][C:32]=2Br)[O:29][CH2:28][C:27]2[N:22]3[CH:23]([CH3:35])[C:24](=[O:34])[NH:25][N:26]=2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].CC1(C)CC(C)OB([C:44]([C:46]([F:49])([F:48])[F:47])=[CH2:45])O1.CCOC(C)=O>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16]([NH:18][C:19]2[CH:20]=[C:21]3[C:30](=[CH:31][C:32]=2[C:44]([C:46]([F:49])([F:48])[F:47])=[CH2:45])[O:29][CH2:28][C:27]2[N:22]3[CH:23]([CH3:35])[C:24](=[O:34])[NH:25][N:26]=2)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 164142704,4,6-Trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinaneHCID 867272933-(7-Bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867274573-[4-Methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl esterYield 68%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of K2CO3 (0.12 g, 0.86 mmol), Pd(PPh3)4 (0.099 g, 0.086 mmol), 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester ((Example 1, Step B, 0.20 g, 0.43 mmol) and 4,4,6-trimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1,3,2-dioxaborinane (0.38 g, 1.7 mmol) in DME (15 mL) and water (2.5 mL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature. EtOAc (50 mL) and water (30 mL) were added and the organic portion was separated, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether) to give 3-[4-methyl-3-oxo-7-(1-trifluoromethyl-vinyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (0.14 g, 68%). 1H NMR (CDCl3, 400 MHz): δ 8.14 (brs, 1H), 6.83 (s, 1H), 6.28 (s, 1H), 5.92 (s, 1H), 5.73 (s, 1H), 4.66 (q, J=6.8 Hz, 1H), 4.56 (d, J=12.8 Hz, 2H), 4.26 (m, 2H), 4.16 (m, 1H), 4.04 (m, 1H), 3.70 (m, 2H), 1.53 (t, J=6.8 Hz, 3H), 1.48 (s, 9H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe organic portion was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC (eluting with 50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-6941dcfe1010437ca0411915620039c8
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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