Methanol → HCID 56932275, compound

HRID 472813Notes

Reaction equation

HRID 472813 reaction equation
CO.[C:3]([O:7][C@H:8]([C:13]1[C:14]([CH3:40])=[N:15][C:16]2[N:17]([N:31]=[C:32]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:33]=2)[C:18]=1[C:19]1[C:20]([CH3:30])=[C:21]2[C:26](=[C:27]([F:29])[CH:28]=1)[O:25][CH2:24][CH2:23][CH2:22]2)[C:9]([O:11]C)=[O:10])([CH3:6])([CH3:5])[CH3:4]>C(=O)=O>[C:3]([O:7][C@H:8]([C:13]1[C:14]([CH3:40])=[N:15][C:16]2[N:17]([N:31]=[C:32]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:33]=2)[C:18]=1[C:19]1[C:20]([CH3:30])=[C:21]2[C:26](=[C:27]([F:29])[CH:28]=1)[O:25][CH2:24][CH2:23][CH2:22]2)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 887MethanolHCID 66693543HCID 66693543, compound

Product 1

HCID 56932275HCID 56932275, compound

Reagents, catalysts & solvents 1

HCID 280Carbon DioxideSolvent

Procedure

The title compound was synthesized using a two step method starting from the racemic ester precursor for Example 39. The racemic ester was separated into two enantiomers using a chiral column and (2R)-methyl 2-tert-butoxy-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate was isolated. Chiral separation method: Chiralpak AD-H preparative column, 20×250 mm, 5 μm to give two enantiomers. Mobile Phase: 15% MeOH in CO2 @ 150 Bar. Temp: 35° C. Flow rate: 45.0 mL/min. for 14 min. UV was monitored @ 254 nm. Hydrolysis of (2R)-methyl 2-tert-butoxy-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate as described in Example 1 provided the title compound with 100% enantiomeric excess. Retention time: 9.94 min. Chiral SFC method: Chiralpak AD-H analytical column, 4.6×250 mm, 5 μm. Mobile Phase: 15% MeOH in CO2. Temp: 35° C. Flow rate: 2.0 mL/min. for 14 min. UV monitored @ 254 nm.

Workup

  1. customChiral separation method
  2. customChiralpak AD-H preparative column, 20×250 mm, 5 μm to give two enantiomers
  3. custom35° C

Sources & evidence

ORD record
ord-8ad988abfb604200b5f05a95db7ae2a1
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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