3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide → 3-{[4-(Azetidin-1-ylcarbonyl)-2-fluorophenyl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 20520Notes

Reaction equation

HRID 20520 reaction equation
[N:1]1([C:5]([C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:25]=[C:26]([O:28][C@@H:29]([CH3:39])[CH2:30][O:31][Si](C(C)(C)C)(C)C)[CH:27]=3)[C:15]([NH:17][C:18]3[CH:23]=[N:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])=[C:9]([F:42])[CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1>CO.Cl>[N:1]1([C:5]([C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:13]=[C:14]([CH:25]=[C:26]([O:28][C@@H:29]([CH3:39])[CH2:30][OH:31])[CH:27]=3)[C:15]([NH:17][C:18]3[CH:23]=[N:22][C:21]([CH3:24])=[CH:20][N:19]=3)=[O:16])=[C:9]([F:42])[CH:8]=2)=[O:6])[CH2:2][CH2:3][CH2:4]1

Participants

4

Reactant 1

HCID 593468603-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 115331033-{[4-(Azetidin-1-ylcarbonyl)-2-fluorophenyl]oxy}-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A mixture of 3-[4-(azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-N-(5-methylpyrazin-2-yl)benzamide (3.6 g, 5.96 mmol) in methanol (60 mL) and 1M hydrochloric acid (60 mL) was stirred for 30 mins at RT. The volatiles were removed in vacuo and the residue adjusted to pH6 with saturated aqueous sodium bicarbonate solution then extracted into ethyl acetate (3×100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and the solvents removed in vacuo. 10% Methanol in ethyl acetate was added and a white solid filtered off. This was crystallised from ethyl acetate/methanol to give the desired compound. (1.24 g), mpt 172° C. The data was in agreement with samples prepared through alternative routes.

Workup

  1. customThe volatiles were removed in vacuo
  2. extractionthen extracted into ethyl acetate (3×100 mL)
  3. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents removed in vacuo
  7. addition10% Methanol in ethyl acetate was added
  8. filtrationa white solid filtered off
  9. customThis was crystallised from ethyl acetate/methanol

Sources & evidence

ORD record
ord-7b44f4c4550c4259a865e69abacb08ca
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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