Triethylamine → HCID 67278772, compound

HRID 1943285Notes

Reaction equation

HRID 1943285 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2([OH:21])[CH2:17][CH:16]([C:18](O)=[O:19])[CH2:15]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1.Cl.[O:23]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH2:27][NH:26][CH2:25][CH2:24]1.C(N(CC)CC)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[OH-].[Na+]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]2([OH:21])[CH2:15][CH:16]([C:18]([N:26]3[CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[O:23][CH2:24][CH2:25]3)=[O:19])[CH2:17]2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]1[CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 111923Propylphosphonic anhydrideHCID 222379922,3,4,5-Tetrahydro-1,4-benzoxazepine--hydrogen chloride (1/1)HCID 574858713-(3-Chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

Product 1

HCID 67278772HCID 67278772, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of crude intermediate 17, 3-(3-chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid (˜4.3 mL ˜0.65 mmol) was added 2,3,4,5-tetrahydro-benzo[f][1,4]oxazepine hydrochloride (239 mg, 1.29 mmol), triethylamine (0.18 ml, 1.29 mmol) and T3P (50% solution in EtOAc, 0.62 ml, 0.97 mmol). The resulting reaction mixture was stirred at RT for 1 hr and then 25 ml of 1N NaOH and 100 ml of EtOAc were added and the layers were separated. The aqueous layer was subjected to EtOAc extraction (2×60 ml) again and the combined organic layers were dried over MgSO4 and evaporated. The residue was purified by flash column chromatography using a 40 g ISCO™ column, eluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH. The product containing fractions were collected and concentrated under reduced pressure to give the title compound 104 mg, 37% yield. Rf=0.50 (15% MeOH/CH2Cl2+0.2% NH4OH); LRMS m/z Calcd for C25H29Cl N2 O3, 440.9, found, 441.2 (M+1) APCI; 100 MHz 13C NMR (CDCl3) 1:1 mixture of rotomers, diagnostic peaks, δ 175.4, 173.9, 159.5, 159.3, 134.2, 134.1, 131.4, 131.3, 122.0, 121.3, 121.0, 74.9, 72.6, 72.2, 56.3, 54.1, 53.9, 49.3, 48.7, 41.2, 41.0, 28.8, 28.5, 23.7, 23.6.

Workup

  1. customThe resulting reaction mixture
  2. customthe layers were separated
  3. extractionThe aqueous layer was subjected to EtOAc extraction (2×60 ml) again
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. customevaporated
  6. customThe residue was purified by flash column chromatography
  7. washeluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3b10668b84d4079b9567b2eaa082ece
Source dataset
uspto-grants-2013_03
Patent number
US08389743B2

Reaction notes

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