Sodium Bicarbonate → (9-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446429

Reaction equation

HRID 446429 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][C:11]1[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH:14]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH:27]([C:30]1[S:31][CH:32]=[C:33]([C:35]([N:37]2[CH2:42][C:41]3([CH2:47][CH2:46][NH:45][CH2:44][CH2:43]3)[O:40][CH2:39][CH2:38]2)=[O:36])[N:34]=1)([CH3:29])[CH3:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(O)(=O)C.O>[Si:1]([O:8][CH2:9][CH2:10][C:11]1[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14][N:45]1[CH2:46][CH2:47][C:41]2([O:40][CH2:39][CH2:38][N:37]([C:35]([C:33]3[N:34]=[C:30]([CH:27]([CH3:28])[CH3:29])[S:31][CH:32]=3)=[O:36])[CH2:42]2)[CH2:43][CH2:44]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579891643-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzaldehyde2×HCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 58168600(9-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzaldehyde [Aromatic Intermediate 5] (4.07 g) was added to (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate [Example 1, step b] (6.10 g) in a mixture of N-methyl-2-pyrrolidinone (50 mL) and acetic acid (0.83 mL) and stirred for 30 min. Sodium triacetoxyborohydride (4.58 g) was then added and the mixture stirred overnight. The reaction mixture was poured into water (100 mL), the pH was adjusted to 8 using saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (3×100 mL). The combined organic phases were washed with water (3×100 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by flash silica chromatography using 77.5:17.5:5 isohexane:ethyl acetate:triethylamine as solvent to give the subtitled compound as a clear oil. Yield 5.35 g.

Workup

  1. stirringthe mixture stirred overnight
  2. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic phases were washed with water (3×100 mL) and brine (100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash silica chromatography

Sources & evidence

ORD record
ord-92c9d161fa2e49ab8fc5cf6638fabb30
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Linked notes

Loading…