Lithium Hydroxide → [2-Carbamoyl-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-4-yl]-acetic acid

HRID 575126Notes

Reaction equation

HRID 575126 reaction equation
C[O:2][C:3](=[O:28])[CH2:4][CH:5]1[C:14]2[S:13][C:12]([C:15](=[O:17])[NH2:16])=[N:11][C:10]=2[C:9]2[CH:18]=[C:19]([C:22]#[C:23][C:24]([OH:27])([CH3:26])[CH3:25])[CH:20]=[CH:21][C:8]=2[O:7][CH2:6]1.[Li+].[OH-]>CO>[C:15]([C:12]1[S:13][C:14]2[CH:5]([CH2:4][C:3]([OH:28])=[O:2])[CH2:6][O:7][C:8]3[CH:21]=[CH:20][C:19]([C:22]#[C:23][C:24]([OH:27])([CH3:26])[CH3:25])=[CH:18][C:9]=3[C:10]=2[N:11]=1)(=[O:17])[NH2:16]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86693150[2-Carbamoyl-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-4-yl]-acetic acid methyl ester

Product 1

HCID 86693151[2-Carbamoyl-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-4-yl]-acetic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of [2-Carbamoyl-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-4-yl]-acetic acid methyl ester in MeOH (5 mL) was added 4 mol/L aqueous solution of LiOH (0.2 mL) and the reaction mixture was stirred at room temperature for 2 h. Then the mixture was partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, concentrated in vacuo, and triturated with EtOAc and hexane (1:1) to afford [2-Carbamoyl-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-4-yl]-acetic acid (20 mg) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 12.66 (br, 1H), 8.61 (d, J=2.2 Hz, 1H), 8.46 (s, 1H), 7.88 (s, 1H), 7.28 (dd, J1=8.36 Hz, J2=2.2 Hz, 1H), 7.04 (d, J=8.4 Hz, 1H), 5.45 (s, 1H), 4.5 (m, 1H), 4.16 (m, 1H), 2.72 (m, 1H), 2.62 (m, 1H), 1.48 (s, 6H); LC-MS (ESI & APCI): 387.6 (M+1).

Workup

  1. customThen the mixture was partitioned between EtOAc and H2O
  2. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customtriturated with EtOAc and hexane (1:1)

Sources & evidence

ORD record
ord-3773f11d7c5d44c2bbff552c2871407c
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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