Water → HCID 11268869, compound

HRID 30327Notes

Reaction equation

HRID 30327 reaction equation
[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([O:31][CH3:32])=[C:7]([CH2:9][C:10]([CH:18]2[O:23][CH2:22][CH2:21][N:20](CC3C=CC=CC=3)[CH2:19]2)([CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[OH:11])[CH:8]=1.O>C(O)(C)C>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([O:31][CH3:32])=[C:7]([CH2:9][C:10]([CH:18]2[O:23][CH2:22][CH2:21][NH:20][CH2:19]2)([CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[OH:11])[CH:8]=1

Participants

4

Reactant 2

HCID 962WaterHCID 68435065HCID 68435065, compound

Product 1

HCID 11268869HCID 11268869, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

A 6 L Parr bottle is loaded with 51b (1021 g), i-propanol (3630 mL) and water (639 mL). After purging with N2, 5% Pd—C 52% wet is added (105.6 g) and the mixture is then pressurized with hydrogen (50 psi). The reaction mixture is shaken for 9 h 30 mins, then the mixture is filtered on a Hyflo Super Cel® pad (100 g) pre-imbibed with 80/20 i-propanol/water (500 mL). The catalyst is rinsed with a 80:20: i-propanol:water mixture (500 mL). The solvents are stripped off then i-propanol is added (2000 mL) to be partially removed again. Then i-propanol is re-added (1400 mL) and the heterogeneous mixture is concentrated to provide an off-white solid To this crude alcohol 52b is added i-propanol (4474 mL) and the mixture is heated to reflux until a homogeneous solution is formed. Then, the mixture is cooled slowly and the crystallization starts at 60° C. The powder is filtered at room temperature, rinsed with i-propanol (2×350 mL) and dried under reduced pressure at 40° C. to give highly pure compound 52b with 80% recovery yield (98.4% de, 99.2% ee).

Workup

  1. customAfter purging with N2, 5% Pd—C 52%
  2. additionwet is added (105.6 g)
  3. filtrationthe mixture is filtered on a Hyflo Super Cel® pad (100 g) pre-imbibed with 80/20 i-propanol/water (500 mL)
  4. washThe catalyst is rinsed with a 80:20
  5. additioni-propanol is added (2000 mL)
  6. customto be partially removed again
  7. additionThen i-propanol is re-added (1400 mL)
  8. concentrationthe heterogeneous mixture is concentrated
  9. customto provide an off-white solid To this crude alcohol 52b
  10. temperaturethe mixture is heated
  11. temperatureto reflux until a homogeneous solution
  12. customis formed
  13. temperatureThen, the mixture is cooled slowly
  14. customthe crystallization
  15. customstarts at 60° C
  16. filtrationThe powder is filtered at room temperature
  17. washrinsed with i-propanol (2×350 mL)
  18. customdried under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-e293d63c566d4f8794a91ae7715ec2b4
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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