Acetic Acid → (9-(2-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471063

Reaction equation

HRID 471063 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][OH:26])=[CH:20][C:17]=1[CH:18]=O.FC(F)(F)C(O)=O.[CH:34]([C:37]1[S:38][CH:39]=[C:40]([C:42]([N:44]2[CH2:49][C:48]3([CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[O:47][CH2:46][CH2:45]2)=[O:43])[N:41]=1)([CH3:36])[CH3:35].C(O)(=O)C>CN1C(=O)CCC1.C(OCC)(=O)C>[F:15][C:16]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][OH:26])=[CH:20][C:17]=1[CH2:18][N:52]1[CH2:53][CH2:54][C:48]2([O:47][CH2:46][CH2:45][N:44]([C:42]([C:40]3[N:41]=[C:37]([CH:34]([CH3:35])[CH3:36])[S:38][CH:39]=3)=[O:43])[CH2:49]2)[CH2:50][CH2:51]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydride2×HCID 579893302-Fluoro-5-(2-hydroxyethyl)benzaldehyde2×HCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989245(9-(2-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Sodium triacetoxyborohydride (0.339 g) was added to a stirred solution of 2-fluoro-5-(2-hydroxyethyl)benzaldehyde (example 40, step a) (0.135 g), (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.339 g) and acetic acid (0.046 mL) in NMP (7 mL). After 16 h, more 2-fluoro-5-(2-hydroxyethyl)benzaldehyde (example 40, step a) (0.135 g) was added followed by sodium triacetoxyborohydride (0.339 g). After 2 h, the reaction mixture was diluted with ethyl acetate (60 mL) and washed with saturated sodium bicarbonate solution (30 mL). The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate solution was evaporated in vacuo. Purification was by silica gel chromatography eluting with ethyl acetate:triethylamine, 10:1 to give the subtitled compound as a gum that contained NMP. The NMP was removed by applying the gum to a 10 g SCX cartridge eluting first with methanol and then 20% ‘880’ aqueous ammonia in methanol to collect the subtitled compound. The solution was evaporated to dryness and the resulting gum applied to a silica gel column eluting with ethyl acetate:triethylamine, 10:1 to give the subtitled compound as a gum. Yield 0.31 g.

Workup

  1. waitAfter 2 h
  2. washwashed with saturated sodium bicarbonate solution (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. customThe combined ethyl acetate solution was evaporated in vacuo
  5. customPurification
  6. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-6315c35740d4409582f798926d9fd44d
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Linked notes

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