Water → HCID 46926793, compound

HRID 473959Notes

Reaction equation

HRID 473959 reaction equation
O.[OH-].[Li+].[CH3:4][C:5]([CH3:37])([CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]3[N:26]([C:27](=[O:35])[NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:25][CH2:24][O:23][C:22]=3[CH:36]=2)=[CH:14][N:13]=1)[C:6]([O:8]C)=[O:7].O1CCCC1.O>CO>[CH3:4][C:5]([CH3:37])([CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]3[N:26]([C:27](=[O:35])[NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH2:25][CH2:24][O:23][C:22]=3[CH:36]=2)=[CH:14][N:13]=1)[C:6]([OH:8])=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrate2×HCID 58577872HCID 58577872, compound

Product 1

HCID 46926793HCID 46926793, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Lithium hydroxide monohydrate (14.3 mg, 0.342 mmol) was added to a solution of methyl 2,2-dimethyl-3-(5-(4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)propanoate B-3 (ca. 62.0 mg, 0.114 mmol) in 1:1:1 tetrahydrofuran:water:methanol (1.14 mL) at room temperature. After 12 h of vigorous stirring at room temperature, lithium hydroxide monohydrate (14.3 mg, 0.342 mmol) was added, and the reaction mixture was heated at 65° C. under microwave irradiation for 30 mins. The clear solution was then quenched with a 1 N aqueous solution of hydrogen chloride (1.0 mL) and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid) to give white crystalline 2,2-dimethyl-3-(5-(4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)propanoic acid B-4 (36.6 mg, Yield=72% over 2 steps). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23 (s, 6H), 3.88 (t, J=4.10 Hz, 2H), 4.28 (s, 2H), 4.30 (t, J=4.10 Hz, 2H), 6.86 (d, J=8.51 Hz, 1H), 7.01 (dt, J=1.10, 7.41 Hz, 1H), 7.16-7.21 (m, 2H), 7.29 (t, J=7.72 Hz, 2H), 7.50 (d, J=8.20 Hz, 2H), 7.60 (d, J=8.51 Hz, 1H), 7.98 (br d, J=8.51 Hz, 1H), 8.44 (s, 1H), 9.16 (s, 1H), 12.37 (br s, 1H); MS (ESI) [M+1]+ 448.

Workup

  1. customat room temperature
  2. temperaturethe reaction mixture was heated at 65° C. under microwave irradiation for 30 mins
  3. customThe clear solution was then quenched with a 1 N aqueous solution of hydrogen chloride (1.0 mL)
  4. concentrationconcentrated to dryness under reduced pressure
  5. customThe crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid)

Sources & evidence

ORD record
ord-74883c0275b44ec88a7289b57dbe7aab
Source dataset
uspto-grants-2014_01
Patent number
US08637507B2

Reaction notes

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