Acetic Acid → (9-(2,3-Difluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone

HRID 471035Notes

Reaction equation

HRID 471035 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C:9]1[S:13][C:12]([C:14]([N:16]2[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[O:19][CH2:18][CH2:17]2)=[O:15])=[CH:11][CH:10]=1.[F:27][C:28]1[C:35]([F:36])=[CH:34][C:33]([CH2:37][CH2:38][OH:39])=[CH:32][C:29]=1[CH:30]=O.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[F:27][C:28]1[C:35]([F:36])=[CH:34][C:33]([CH2:37][CH2:38][OH:39])=[CH:32][C:29]=1[CH2:30][N:24]1[CH2:25][CH2:26][C:20]2([O:19][CH2:18][CH2:17][N:16]([C:14]([C:12]3[S:13][C:9]([CH3:8])=[CH:10][CH:11]=3)=[O:15])[CH2:21]2)[CH2:22][CH2:23]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 579891022,3-Difluoro-5-(2-hydroxyethyl)benzaldehydeHCID 67292300(5-Methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57988906(9-(2,3-Difluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(5-methylthiophen-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(5-Methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 9, step b) (0.53 g) was added to a solution of 2,3-difluoro-5-(2-hydroxyethyl)benzaldehyde (example 32, step b) (0.25 g) and acetic acid (0.08 mL) in methanol (5 mL). The reaction was stirred for 30 min and cooled in an ice bath. Sodium cyanoborohydride (0.13 g) was then added, the mixture allowed to warm to RT and stirred for 18 h. The reaction was concentrated in vacuo. Purification was by silica gel chromatography eluting with 99:1:0.1 to 97:3:0.3 DCM:methanol:‘880’ aqueous ammonia gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a gum. Yield 0.08 g.

Workup

  1. temperaturecooled in an ice bath
  2. stirringstirred for 18 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customPurification
  5. washeluting with 99:1:0.1 to 97:3:0.3 DCM
  6. additionThe fractions containing product
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-769cbfe0950b44d19a184d94401d6f24
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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