Sodium Hydroxide → (3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid

HRID 1527574Notes

Reaction equation

HRID 1527574 reaction equation
C[O:2][C:3](=[O:39])[CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([C:36](=[O:38])[NH2:37])=[CH:11][N:12]2[CH2:15][C:16]([N:18]2[CH2:22][C@H:21]([F:23])[CH2:20][C@H:19]2[C:24](=[O:35])[NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=2[F:34])=[O:17])=[CH:8][CH:7]=1.[OH-].[Na+]>C1COCC1.O>[C:36]([C:10]1[C:9]2[C:13](=[CH:14][C:6]([O:5][CH2:4][C:3]([OH:39])=[O:2])=[CH:7][CH:8]=2)[N:12]([CH2:15][C:16]([N:18]2[CH2:22][C@H:21]([F:23])[CH2:20][C@H:19]2[C:24](=[O:35])[NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=2[F:34])=[O:17])[CH:11]=1)(=[O:38])[NH2:37]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 68283320(3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester

Product 1

HCID 68283430(3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester Example 592 (18 mg, 0.032 mmol) in a mixture of THF (2 mL) and water (0.2 mL) was added 1N NaOH (0.064 mL), followed by stirring at RT for 4 h. The reaction mixture was partitioned between CH2Cl2 and water. The aqueous phase was adjusted to pH=2 by addition of 1N HCl, followed by extraction with CH2Cl2 (3×). The combined organics were dried (phase separator) and concentrated under reduced pressure to afford the title compound as a white solid. MS: 549 [M+H]+; tR (HPLC conditions c): 3.74 min.

Workup

  1. customThe reaction mixture was partitioned between CH2Cl2 and water
  2. additionThe aqueous phase was adjusted to pH=2 by addition of 1N HCl
  3. extractionfollowed by extraction with CH2Cl2 (3×)
  4. customThe combined organics were dried (phase separator)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bf963abc77fb4ac7b6a831b561faf030
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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