Trifluoroacetic acid → 1'-({1-[4-(difluoromethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-one TFA salt

HRID 504282Notes

Reaction equation

HRID 504282 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[F:28][CH:29]([F:43])[O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2([C:40]([OH:42])=O)[CH2:39][CH2:38]2)=[CH:33][CH:32]=1.Cl.Cl.[NH:46]1[CH2:50][CH2:49][C:48]2([C:58]3[CH:57]=[CH:56][N:55]=[CH:54][C:53]=3[C:52](=[O:59])[O:51]2)[CH2:47]1.CN1CCOCC1.[C:67]([OH:73])([C:69]([F:72])([F:71])[F:70])=[O:68]>CN(C=O)C>[OH:73][C:67]([C:69]([F:72])([F:71])[F:70])=[O:68].[F:43][CH:29]([F:28])[O:30][C:31]1[CH:32]=[CH:33][C:34]([C:37]2([C:40]([N:46]3[CH2:50][CH2:49][C:48]4([C:58]5[CH:57]=[CH:56][N:55]=[CH:54][C:53]=5[C:52](=[O:59])[O:51]4)[CH2:47]3)=[O:42])[CH2:38][CH2:39]2)=[CH:35][CH:36]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 289377331-[4-(Difluoromethoxy)phenyl]cyclopropanecarboxylic acidHCID 666621753H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-one dihydrochloride

Product 1

HCID 866022721'-({1-[4-(difluoromethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3'-pyrrolidin]-3-one TFA salt

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

BOP (0.18 g, 0.42 mmol) was added to a mixture of 1-[4-(difluoromethoxy)phenyl]cyclopropanecarboxylic acid (0.10 g, 0.46 mmol) and 3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one dihydrochloride (0.10 g, 0.38 mmol) in DMF (2.5 mL). After 5 min, 4-methylmorpholine (0.2 mL, 2.0 mmol) was added to the mixture. The resulting mixture was stirred at room temperature overnight, then was adjusted to be acidic (pH=2.0) with TFA, and then was purified by prep-LCMS to give 1′-({1-[4-(difluoromethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one TFA salt. The purified salt was neutralized by an addition of NaHCO3 aqueous solution (7.5%). The mixture was extracted with ethyl acetate and the organic phase was concentrated to give 1′-({1-[4-(difluoromethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one. The desired stereo-isomer was isolated by chiral column to afford (1R)-1′-({1-[4-(difluoromethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[furo[3,4-c]pyridine-1,3′-pyrrolidin]-3-one (49.5 mg, 31%).

Workup

  1. customwas purified by prep-LCMS

Sources & evidence

ORD record
ord-13f3535a1bba4e6b9b916fbee16766be
Source dataset
uspto-grants-2010_08
Patent number
US07776874B2

Reaction notes

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